Proposed Changes to the Enzyme List

References:

1.	Cooper, R.A. The pathway for L-galactonate catabolism in Escherichia coli K-12. FEBS Lett. 103 (1979) 216–220. [PMID: 381020]
2.	Kuivanen, J. and Richard, P. The yjjN of E. coli codes for an L-galactonate dehydrogenase and can be used for quantification of L-galactonate and L-gulonate. Appl. Biochem. Biotechnol. 173 (2014) 1829–1835. [PMID: 24861318]
3.	Hobbs, M.E., Williams, H.J., Hillerich, B., Almo, S.C. and Raushel, F.M. L-Galactose metabolism in Bacteroides vulgatus from the human gut microbiota. Biochemistry 53 (2014) 4661–4670. [DOI] [PMID: 24963813]

[EC 1.1.1.414 created 2018]

1.3.3.9

Transferred entry:

secologanin synthase. Now EC 1.14.19.62, secologanin synthase

[EC 1.3.3.9 created 2002, deleted 2018]

1.6.1.5

Transferred entry:

proton-translocating NAD(P)⁺ transhydrogenase. Now EC 7.1.1.1, proton-translocating NAD(P)⁺ transhydrogenase

[EC 1.6.1.5 created 2015, deleted 2018]

1.6.5.3

Transferred entry:

NADH:ubiquinone reductase (H⁺-translocating). Now EC 7.1.1.2, NADH:ubiquinone reductase (H⁺-translocating)

[EC 1.6.5.3 created 1961, deleted 1965, reinstated 1983, modified 2011, modified 2013, deleted 2018]

1.6.5.8

Transferred entry:

NADH:ubiquinone reductase (Na⁺-transporting). Now EC 7.2.1.1, NADH:ubiquinone reductase (Na⁺-transporting)

[EC 1.6.5.8 created 2011, deleted 2018]

1.13.11.86

Accepted name:

5-aminosalicylate 1,2-dioxygenase

Reaction:

5-aminosalicylate + O₂ = (2Z,4E)-4-amino-6-oxohepta-2,4-dienedioate

Glossary:

5-aminosalicylate = 5-amino-2-hydroxybenzoate

Other name(s):

mabB (gene name)

Systematic name:

5-aminosalicylate:oxygen 1,2-oxidoreductase (ring-opening)

Comments:

Requires iron(II). The enzyme, characterized from different bacteria, is a nonheme iron dioxygenase in the bicupin family.

Links to other databases:

References:

1.	Stolz, A., Nortemann, B. and Knackmuss, H.J. Bacterial metabolism of 5-aminosalicylic acid. Initial ring cleavage. Biochem. J. 282 (1992) 675–680. [PMID: 1554350]
2.	Yu, H., Zhao, S. and Guo, L. Novel gene encoding 5-aminosalicylate 1,2-dioxygenase from Comamonas sp. strain QT12 and catalytic properties of the purified enzyme. J. Bacteriol. 200 (2018) . [PMID: 29038259]

[EC 1.13.11.86 created 2018]

1.14.13.11

Transferred entry:

trans-cinnamate 4-monooxygenase. Now EC 1.14.14.91, trans-cinnamate 4-monooxygenase

[EC 1.14.13.11 created 1976, deleted 2018]

1.14.13.12

Transferred entry:

benzoate 4-monooxygenase. Now EC 1.14.14.92, benzoate 4-monooxygenase

[EC 1.14.13.12 created 1976, deleted 2018]

1.14.13.28

Transferred entry:

3,9-dihydroxypterocarpan 6a-monooxygenase. Now EC 1.14.14.93, 3,9-dihydroxypterocarpan 6a-monooxygenase

[EC 1.14.13.28 created 1989, deleted 2018]

1.14.13.30

Transferred entry:

leukotriene-B₄ 20-monooxygenase. Now EC 1.14.14.94, leukotriene-B₄ 20-monooxygenase

[EC 1.14.13.30 created 1989, deleted 2018]

1.14.13.36

Transferred entry:

5-O-(4-coumaroyl)-D-quinate 3′-monooxygenase. Now EC 1.14.14.96, 5-O-(4-coumaroyl)-D-quinate 3′-monooxygenase

[EC 1.14.13.36 created 1990, deleted 2018]

1.14.13.37

Transferred entry:

methyltetrahydroprotoberberine 14-monooxygenase. Now EC 1.14.14.97, methyltetrahydroprotoberberine 14-monooxygenase

[EC 1.14.13.37 created 1990, deleted 2018]

1.14.13.47

Transferred entry:

(S)-limonene 3-monooxygenase. Now EC 1.14.14.99, (S)-limonene 3-monooxygenase

[EC 1.14.13.47 created 1992, modified 2003, deleted 2018]

1.14.13.52

Transferred entry:

isoflavone 3′-hydroxylase. Now EC 1.14.14.88, isoflavone 3′-hydroxylase

[EC 1.14.13.52 created 1992, deleted 2018]

1.14.13.53

Transferred entry:

4′-methoxyisoflavone 2′-hydroxylase. Now EC 1.14.14.89, 4′-methoxyisoflavone 2′-hydroxylase

[EC 1.14.13.53 created 1992, modified 2005, deleted 2018]

1.14.13.55

Transferred entry:

protopine 6-monooxygenase. Now EC 1.14.14.98, protopine 6-monooxygenase

[EC 1.14.13.55 created 1999, deleted 2018]

1.14.13.56

Transferred entry:

dihydrosanguinarine 10-monooxygenase. Now EC 1.14.14.100, dihydrosanguinarine 10-monooxygenase

[EC 1.14.13.56 created 1999, deleted 2018]

1.14.13.57

Transferred entry:

dihydrochelirubine 12-monooxygenase. Now EC 1.14.14.101, dihydrochelirubine 12-monooxygenase

[EC 1.14.13.57 created 1999, deleted 2018]

1.14.13.70

Transferred entry:

sterol 14α-demethylase. Now EC 1.14.14.154, sterol 14α-demethylase

[EC 1.14.13.70 created 2001, modified 2013, deleted 2018]

1.14.13.71

Transferred entry:

N-methylcoclaurine 3′-monooxygenase. Now EC 1.14.14.102, N-methylcoclaurine 3′-monooxygenase

[EC 1.14.13.71 created 2001, deleted 2018]

1.14.13.73

Transferred entry:

tabersonine 16-hydroxylase. Now EC 1.14.14.103, tabersonine 16-hydroxylase

[EC 1.14.13.73 created 2002, deleted 2018]

1.14.13.75

Transferred entry:

vinorine hydroxylase. Now EC 1.14.14.104, vinorine hydroxylase

[EC 1.14.13.75 created 2002, deleted 2018]

1.14.13.76

Transferred entry:

taxane 10β-hydroxylase. Now EC 1.14.14.105, taxane 10β-hydroxylase

[EC 1.14.13.76 created 2002, deleted 2018]

1.14.13.77

Transferred entry:

taxane 13α-hydroxylase. Now EC 1.14.14.106, taxane 13α-hydroxylase

[EC 1.14.13.77 created 2002, deleted 2018]

1.14.13.79

Transferred entry:

ent-kaurenoic acid oxidase. Now EC 1.14.14.107, ent-kaurenoic acid oxidase

[EC 1.14.13.79 created 2002, deleted 2018]

1.14.13.85

Transferred entry:

glyceollin synthase. Now EC 1.14.14.135, glyceollin synthase

[EC 1.14.13.85 created 2004, deleted 2018]

1.14.13.87

Transferred entry:

licodione synthase. Now EC 1.14.14.140, licodione synthase

[EC 1.14.13.87 created 2004, deleted 2018]

1.14.13.89

Transferred entry:

isoflavone 2-hydroxylase. Now EC 1.14.14.90, isoflavone 2-hydroxylase

[EC 1.14.13.89 created 2005, deleted 2018]

1.14.13.91

Transferred entry:

deoxysarpagine hydroxylase. Now EC 1.14.14.136, deoxysarpagine hydroxylase

[EC 1.14.13.91 created 2005, deleted 2018]

1.14.13.93

Transferred entry:

(+)-abscisic acid 8′-hydroxylase. Now EC 1.14.14.137, (+)-abscisic acid 8′-hydroxylase

[EC 1.14.13.93 created 2005, deleted 2018]

1.14.13.94

Transferred entry:

lithocholate 6β-hydroxylase. Now EC 1.14.14.138, lithocholate 6β-hydroxylase

[EC 1.14.13.94 created 2005, deleted 2018]

1.14.13.96

Transferred entry:

5β-cholestane-3α,7α-diol 12α-hydroxylase. Now EC 1.14.14.139, 5β-cholestane-3α,7α-diol 12α-hydroxylase

[EC 1.14.13.96 created 2005, deleted 2018]

1.14.13.102

Transferred entry:

psoralen synthase. Now EC 1.14.14.141, psoralen synthase

[EC 1.14.13.102 created 2007, deleted 2018]

1.14.13.103

Transferred entry:

8-dimethylallylnaringenin 2-hydroxylase. Now EC 1.14.14.142, 8-dimethylallylnaringenin 2-hydroxylase

[EC 1.14.13.103 created 2007, deleted 2018]

1.14.13.104

Transferred entry:

(+)-menthofuran synthase. Now EC 1.14.14.143, (+)-menthofuran synthase

[EC 1.14.13.104 created 2008, deleted 2018]

1.14.13.108

Transferred entry:

abieta-7,13-diene hydroxylase. Now EC 1.14.14.144, abieta-7,13-diene hydroxylase

[EC 1.14.13.108 created 2009, modified 2012, deleted 2018]

1.14.13.109

Transferred entry:

abieta-7,13-dien-18-ol hydroxylase. Now EC 1.14.14.145, abieta-7,13-dien-18-ol hydroxylase

[EC 1.14.13.109 created 2009, modified 2012, deleted 2018]

1.14.13.110

Transferred entry:

geranylgeraniol 18-hydroxylase. Now EC 1.14.14.146, geranylgeraniol 18-hydroxylase

[EC 1.14.13.110 created 2009, deleted 2018]

1.14.13.112

Transferred entry:

3-epi-6-deoxocathasterone 23-monooxygenase. Now EC 1.14.14.147, 3-epi-6-deoxocathasterone 23-monooxygenase

[EC 1.14.13.112 created 2010, deleted 2018]

1.14.13.115

Transferred entry:

angelicin synthase. Now EC 1.14.14.148, angelicin synthase

[EC 1.14.13.115 created 2010, deleted 2018]

1.14.13.119

Transferred entry:

5-epiaristolochene 1,3-dihydroxylase. Now EC 1.14.14.149, 5-epiaristolochene 1,3-dihydroxylase

[EC 1.14.13.119 created 2011, deleted 2018]

1.14.13.120

Transferred entry:

costunolide synthase. Now EC 1.14.14.150, costunolide synthase

[EC 1.14.13.120 created 2011, deleted 2018]

1.14.13.121

Transferred entry:

premnaspirodiene oxygenase. Now EC 1.14.14.151, premnaspirodiene oxygenase

[EC 1.14.13.121 created 2011, deleted 2018]

1.14.13.123

Transferred entry:

germacrene A hydroxylase. Now EC 1.14.14.95, germacrene A hydroxylase

[EC 1.14.13.123 created 2011, deleted 2018]

1.14.13.125

Transferred entry:

tryptophan N-monooxygenase. Now EC 1.14.14.156, tryptophan N-monooxygenase

[EC 1.14.13.125 created 2011, deleted 2018]

1.14.13.133

Transferred entry:

pentalenene oxygenase. Now EC 1.14.15.32, pentalenene oxygenase

[EC 1.14.13.133 created 2011, deleted 2018]

1.14.13.134

Transferred entry:

β-amyrin 11-oxidase. Now EC 1.14.14.152, β-amyrin 11-oxidase

[EC 1.14.13.134 created 2011, deleted 2018]

1.14.13.137

Transferred entry:

indole-2-monooxygenase. Now EC 1.14.14.153, indole-2-monooxygenase

[EC 1.14.13.137 created 2012, deleted 2018]

1.14.13.138

Transferred entry:

indolin-2-one monooxygenase. Now EC 1.14.14.157, indolin-2-one monooxygenase

[EC 1.14.13.138 created 2012, deleted 2018]

1.14.13.139

Transferred entry:

3-hydroxyindolin-2-one monooxygenase. Now EC 1.14.14.109, 3-hydroxyindolin-2-one monooxygenase

[EC 1.14.13.139 created 2012, deleted 2018]

1.14.13.140

Transferred entry:

2-hydroxy-1,4-benzoxazin-3-one monooxygenase. Now EC 1.14.14.110, 2-hydroxy-1,4-benzoxazin-3-one monooxygenase.

[EC 1.14.13.140 created 2012, deleted 2018]

1.14.13.142

Transferred entry:

3-ketosteroid 9α-monooxygenase. Now EC 1.14.15.30, 3-ketosteroid 9α-monooxygenase

[EC 1.14.13.142 created 2012, deleted 2018]

1.14.13.144

Transferred entry:

9β-pimara-7,15-diene oxidase. Now EC 1.14.14.111, 9β-pimara-7,15-diene oxidase.

[EC 1.14.13.144 created 2012, deleted 2018]

1.14.13.145

Transferred entry:

ent-cassa-12,15-diene 11-hydroxylase. Now EC 1.14.14.112, ent-cassa-12,15-diene 11-hydroxylase.

[EC 1.14.13.145 created 2012, deleted 2018]

1.14.13.150

Transferred entry:

α-humulene 10-hydroxylase. Now EC 1.14.14.113, α-humulene 10-hydroxylase.

[EC 1.14.13.150 created 2012, deleted 2018]

1.14.13.156

Transferred entry:

1,8-cineole 2-endo-monooxygenase. Now EC 1.14.14.133, 1,8-cineole 2-endo-monooxygenase

[EC 1.14.13.156 created 2012, deleted 2018]

1.14.13.158

Transferred entry:

amorpha-4,11-diene 12-monooxygenase. Now EC 1.14.14.114, amorpha-4,11-diene 12-monooxygenase.

[EC 1.14.13.158 created 2012, deleted 2018]

1.14.13.162

Transferred entry:

2,5-diketocamphane 1,2-monooxygenase. Now EC 1.14.14.108, 2,5-diketocamphane 1,2-monooxygenase

[EC 1.14.13.162 created 1972 as EC 1.14.15.2, transferred 2012 to EC 1.14.13.162, deleted 2018]

1.14.13.173

Transferred entry:

11-oxo-β-amyrin 30-oxidase. Now EC 1.14.14.115, 11-oxo-β-amyrin 30-oxidase.

[EC 1.14.13.173 created 2013, deleted 2018]

1.14.13.174

Transferred entry:

averantin hydroxylase. Now EC 1.14.14.116, averantin hydroxylase

[EC 1.14.13.174 created 2013, deleted 2018]

1.14.13.175

Transferred entry:

aflatoxin B synthase. Now EC 1.14.14.117, aflatoxin B synthase

[EC 1.14.13.175 created 2013, deleted 2018]

1.14.13.176

Transferred entry:

tryprostatin B 6-hydroxylase. Now EC 1.14.14.118, tryprostatin B 6-hydroxylase

[EC 1.14.13.176 created 2013, deleted 2018]

1.14.13.177

Transferred entry:

fumitremorgin C monooxygenase. Now EC 1.14.14.119, fumitremorgin C monooxygenase

[EC 1.14.13.177 created 2013, deleted 2018]

1.14.13.183

Transferred entry:

dammarenediol 12-hydroxylase. Now EC 1.14.14.120, dammarenediol 12-hydroxylase

[EC 1.14.13.183 created 2013, deleted 2018]

1.14.13.184

Transferred entry:

protopanaxadiol 6-hydroxylase. Now EC 1.14.14.121, protopanaxadiol 6-hydroxylase

[EC 1.14.13.184 created 2013, deleted 2018]

1.14.13.185

Transferred entry:

pikromycin synthase. Now EC 1.14.15.33, pikromycin synthase

[EC 1.14.13.185 created 2014, deleted 2018]

1.14.13.186

Transferred entry:

20-oxo-5-O-mycaminosyltylactone 23-monooxygenase. Now EC 1.14.15.34, 20-oxo-5-O-mycaminosyltylactone 23-monooxygenase

[EC 1.14.13.186 created 2014, deleted 2018]

1.14.13.188

Transferred entry:

6-deoxyerythronolide B hydroxylase. Now EC 1.14.15.35, 6-deoxyerythronolide B hydroxylase

[EC 1.14.13.188 created 2014, deleted 2018]

1.14.13.192

Transferred entry:

oryzalexin E synthase. Now EC 1.14.14.122, oryzalexin E synthase

[EC 1.14.13.192 created 2014, deleted 2018]

1.14.13.193

Transferred entry:

oryzalexin D synthase. Now EC 1.14.14.123, oryzalexin D synthase

[EC 1.14.13.193 created 2014, deleted 2018]

1.14.13.197

Transferred entry:

dihydromonacolin L hydroxylase. Now EC 1.14.14.124, dihydromonacolin L hydroxylase

[EC 1.14.13.197 created 2014, deleted 2018]

1.14.13.198

Transferred entry:

monacolin L hydroxylase. Now EC 1.14.14.125, monacolin L hydroxylase

[EC 1.14.13.198 created 2014, deleted 2018]

1.14.13.201

Transferred entry:

β-amyrin 28-monooxygenase. Now EC 1.14.14.126, β-amyrin 28-monooxygenase

[EC 1.14.13.201 created 2015, deleted 2018]

1.14.13.202

Transferred entry:

methyl farnesoate epoxidase. Now EC 1.14.14.127, methyl farnesoate epoxidase

[EC 1.14.13.202 created 2015, deleted 2018]

1.14.13.203

Transferred entry:

farnesoate epoxidase. Now EC 1.14.14.128, farnesoate epoxidase

[EC 1.14.13.203 created 2015, deleted 2018]

1.14.13.204

Transferred entry:

long-chain acyl-CoA ω-monooxygenase. Now EC 1.14.14.129, long-chain acyl-CoA ω-monooxygenase

[EC 1.14.13.204 created 2015, deleted 2018]

1.14.13.206

Transferred entry:

laurate 7-monooxygenase. Now EC 1.14.14.130, laurate 7-monooxygenase

[EC 1.14.13.206 created 2015, deleted 2018]

1.14.13.213

Transferred entry:

bursehernin 5-monooxygenase. Now EC 1.14.14.131, bursehernin 5-monooxygenase

[EC 1.14.13.213 created 2016, deleted 2018]

1.14.13.214

Transferred entry:

(–)-4′-demethyl-deoxypodophyllotoxin 4-hydroxylase. Now EC 1.14.14.132, (–)-4′-demethyl-deoxypodophyllotoxin 4-hydroxylase

[EC 1.14.13.214 created 2016, deleted 2018]

1.14.14.88

Accepted name:

isoflavone 3′-hydroxylase

Reaction:

formononetin + [reduced NADPH—hemoprotein reductase] + O₂ = calycosin + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of medicarpin and formononetin derivatives biosynthesis, click here

Glossary:

calycosin = 3′-hydroxyformononetin

Other name(s):

isoflavone 3′-monooxygenase; CYP81E9

Systematic name:

formononetin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (3′-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. Also acts on biochanin A and other isoflavones with a 4′-methoxy group. Involved in the biosynthesis of the pterocarpin phytoalexins medicarpin and maackiain.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 110183-50-1

References:

1.	Hinderer, W., Flentje, U. and Barz, W. Microsomal isoflavone 2′-hydroxylases and 3′-hydroxylases from chickpea (Cicer arietinum L) cell-suspensions induced for pterocarpan phytoalexin formation. FEBS Lett. 214 (1987) 101–106.

[EC 1.14.14.88 created 1992 as EC 1.14.13.52, transferred 2018 to EC 1.14.14.88]

1.14.14.89

Accepted name:

4′-methoxyisoflavone 2′-hydroxylase

Reaction:

formononetin + [reduced NADPH—hemoprotein reductase] + O₂ = 2′-hydroxyformononetin + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of the biosynthesis of formononetin and derivatives, click here

Other name(s):

CYP81E1 (gene name); CYP81E3 (gene name); CYP81E7 (gene name); isoflavone 2′-monooxygenase (ambiguous); isoflavone 2′-hydroxylase (ambiguous)

Systematic name:

formononetin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (2′-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. Acts on isoflavones with a 4′-methoxy group, such as formononetin and biochanin A. Involved in the biosynthesis of the pterocarpin phytoalexins medicarpin and maackiain. EC 1.14.14.90, isoflavone 2′-hydroxylase, is less specific and acts on other isoflavones as well as 4′-methoxyisoflavones.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 110183-49-8

References:

1.	Hinderer, W., Flentje, U. and Barz, W. Microsomal isoflavone 2′-hydroxylases and 3′-hydroxylases from chickpea (Cicer arietinum L) cell-suspensions induced for pterocarpan phytoalexin formation. FEBS Lett. 214 (1987) 101–106.
2.	Akashi, T., Aoki, T. and Ayabe, S.-I. CYP81E1, a cytochrome P₄₅₀ cDNA of licorice (Glycyrrhiza echinata L.), encodes isoflavone 2′-hydroxylase. Biochem. Biophys. Res. Commun. 251 (1998) 67–70. [DOI] [PMID: 9790908]
3.	Liu, C.J., Huhman, D., Sumner, L.W. and Dixon, R.A. Regiospecific hydroxylation of isoflavones by cytochrome p₄₅₀ 81E enzymes from Medicago truncatula. Plant J. 36 (2003) 471–484. [PMID: 14617078]

[EC 1.14.14.89 created 1992 as EC 1.14.13.53, modified 2005, transferred 2018 to EC 1.14.14.89]

1.14.14.90

Accepted name:

isoflavone 2′-hydroxylase

Reaction:

an isoflavone + [reduced NADPH—hemoprotein reductase] + O₂ = a 2′-hydroxyisoflavone + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of the biosynthesis of formononetin and derivatives, click here

Other name(s):

isoflavone 2′-monooxygenase; CYP81E1; CYP Ge-3

Systematic name:

isoflavone,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (2′-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. Acts on daidzein, formononetin and genistein. EC 1.14.14.89, 4′-methoxyisoflavone 2′-hydroxylase, has the same reaction but is more specific as it requires a 4′-methoxyisoflavone.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 110183-49-8

References:

1.	Akashi, T., Aoki, T. and Ayabe, S.-I. CYP81E1, a cytochrome P₄₅₀ cDNA of licorice (Glycyrrhiza echinata L.), encodes isoflavone 2′-hydroxylase. Biochem. Biophys. Res. Commun. 251 (1998) 67–70. [DOI] [PMID: 9790908]

[EC 1.14.14.90 created 2005 as EC 1.14.13.89, transferred 2018 to EC 1.14.14.90]

1.14.14.91

Accepted name:

trans-cinnamate 4-monooxygenase

Reaction:

trans-cinnamate + [reduced NADPH—hemoprotein reductase] + O₂ = 4-hydroxycinnamate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of chalcone and stilbene biosynthesis, click here

Other name(s):

cinnamic acid 4-hydroxylase; CA4H; cytochrome P450 cinnamate 4-hydroxylase; cinnamate 4-hydroxylase; cinnamate 4-monooxygenase; cinnamate hydroxylase; cinnamic 4-hydroxylase; cinnamic acid 4-monooxygenase; cinnamic acid p-hydroxylase; t-cinnamic acid hydroxylase; trans-cinnamate 4-hydroxylase; trans-cinnamic acid 4-hydroxylase; CYP73A1 (gene name)

Systematic name:

trans-cinnamate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (4-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein found in plants. The enzyme is involved in flavonoid biosynthesis.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9077-75-2

References:

1.	Potts, J.R.M., Weklych, R. and Conn, E.E. The 4-hydroxylation of cinnamic acid by sorghum microsomes and the requirement for cytochrome P-450. J. Biol. Chem. 249 (1974) 5019–5026. [PMID: 4153152]
2.	Russell, D.W. and Conn, E.E. The cinnamic acid 4-hydroxylase of pea seedlings. Arch. Biochem. Biophys. 122 (1967) 256–268. [DOI] [PMID: 4383827]
3.	Pierrel, M.A., Batard, Y., Kazmaier, M., Mignotte-Vieux, C., Durst, F. and Werck-Reichhart, D. Catalytic properties of the plant cytochrome P450 CYP73 expressed in yeast. Substrate specificity of a cinnamate hydroxylase. Eur. J. Biochem. 224 (1994) 835–844. [PMID: 7925408]

[EC 1.14.14.91 created 1976 as EC 1.14.13.11, transferred 2018 to EC 1.14.14.91]

1.14.14.92

Accepted name:

benzoate 4-monooxygenase

Reaction:

benzoate + [reduced NADPH—hemoprotein reductase] + O₂ = 4-hydroxybenzoate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of benzoate metabolism, click here

Other name(s):

benzoic acid 4-hydroxylase; benzoate 4-hydroxylase; benzoic 4-hydroxylase; benzoate-p-hydroxylase; p-hydroxybenzoate hydroxylase; CYP53A1 (gene name)

Systematic name:

benzoate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (4-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein found in Aspergillus fungi.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, CAS registry number: 39391-25-8

References:

1.	Reddy, C.C. and Vaidyanathan, C.S. Purification, properties and induction of a specific benzoate-4-hydroxylase from Aspergillus niger (UBC 814). Biochim. Biophys. Acta 384 (1975) 46–57. [DOI] [PMID: 236777]
2.	Faber, B.W., van Gorcom, R.F. and Duine, J.A. Purification and characterization of benzoate-para-hydroxylase, a cytochrome P450 (CYP53A1), from Aspergillus niger. Arch. Biochem. Biophys. 394 (2001) 245–254. [PMID: 11594739]

[EC 1.14.14.92 created 1976 as EC 1.14.13.12, transferred 2018 to EC 1.14.14.92]

1.14.14.93

Accepted name:

3,9-dihydroxypterocarpan 6a-monooxygenase

Reaction:

(6aR,11aR)-3,9-dihydroxypterocarpan + [reduced NADPH—hemoprotein reductase] + O₂ = (6aS,11aS)-3,6a,9-trihydroxypterocarpan + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of glyceollin biosynthesis (part 2), click here

Other name(s):

3,9-dihydroxypterocarpan 6a-hydroxylase; 3,9-dihydroxypterocarpan 6α-monooxygenase (erroneous); CYP93A1 (gene name)

Systematic name:

(6aR,11aR)-3,9-dihydroxypterocarpan,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (6a-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein found in soybean. The product of the reaction is the biosynthetic precursor of the glyceollin phytoalexins.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 92584-16-2

References:

1.	Hagmann, M.-L., Heller, W. and Grisebach, H. Induction of phytoalexin synthesis in soybean. Stereospecific 3,9-dihydroxypterocarpan 6a-hydroxylase from elicitor-induced soybean cell cultures. Eur. J. Biochem. 142 (1984) 127–131. [DOI] [PMID: 6540173]
2.	Schopfer, C.R., Kochs, G., Lottspeich, F. and Ebel, J. Molecular characterization and functional expression of dihydroxypterocarpan 6a-hydroxylase, an enzyme specific for pterocarpanoid phytoalexin biosynthesis in soybean (Glycine max L.). FEBS Lett. 432 (1998) 182–186. [PMID: 9720921]

[EC 1.14.14.93 created 1989 as EC 1.14.13.28, transferred 2018 to EC 1.14.14.93]

1.14.14.94

Accepted name:

leukotriene-B₄ 20-monooxygenase

Reaction:

(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate + [reduced NADPH—hemoprotein reductase] + O₂ = (6Z,8E,10E,14Z)-(5S,12R)-5,12,20-trihydroxyicosa-6,8,10,14-tetraenoate + [oxidized NADPH—hemoprotein reductase] + H₂O

Other name(s):

leukotriene-B₄ 20-hydroxylase; leucotriene-B4 ω-hydroxylase; LTB4 20-hydroxylase; LTB4 ω-hydroxylase; CYP4F2 (gene name); CYP4F3 (gene name)

Systematic name:

(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (20-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein found in mammals.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 90119-11-2

References:

1.	Romano, M.C., Eckardt, R.D., Bender, P.E., Leonard, T.B., Straub, K.M. and Newton, J.F. Biochemical characterization of hepatic microsomal leukotriene B₄ hydroxylases. J. Biol. Chem. 262 (1987) 1590–1595. [PMID: 3027095]
2.	Shak, S. and Goldstein, I.M. Leukotriene B₄ ω-hydroxylase in human polymorphonuclear leukocytes. Partial purification and identification as a cytochrome P-450. J. Clin. Invest. 76 (1985) 1218–1228. [DOI] [PMID: 4044832]
3.	Soberman, R.J., Harper, T.W., Murphy, R.C. and Austen, K.F. Identification and functional characterization of leukotriene B₄ 20-hydroxylase of human polymorphonuclear leukocytes. Proc. Natl. Acad. Sci. USA 82 (1985) 2292–2295. [DOI] [PMID: 2986111]

[EC 1.14.14.94 created 1989 as EC 1.14.13.30, transferred 2018 to EC 1.14.14.94]

1.14.14.95

Accepted name:

germacrene A hydroxylase

Reaction:

(+)-germacrene A + 3 [reduced NADPH—hemoprotein reductase] + 3 O₂ = germacra-1(10),4,11(13)-trien-12-oate + 3 [oxidized NADPH—hemoprotein reductase] + 4 H₂O (overall reaction)
(1a) (+)-germacrene A + O₂ + [reduced NADPH—hemoprotein reductase] = germacra-1(10),4,11(13)-trien-12-ol + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) germacra-1(10),4,11(13)-trien-12-ol + O₂ + [reduced NADPH—hemoprotein reductase] = germacra-1(10),4,11(13)-trien-12-al + [oxidized NADPH—hemoprotein reductase] + 2 H₂O
(1c) germacra-1(10),4,11(13)-trien-12-al + O₂ + [reduced NADPH—hemoprotein reductase] = germacra-1(10),4,11(13)-trien-12-oate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of costunolide biosynthesis, click here

Other name(s):

GAO (gene name)

Systematic name:

(+)-germacrene-A,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (12-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. This plant enzyme catalyses three steps in a pathway that leads to the biosynthesis of many sesquiterpenoid lactones.

Links to other databases:

References:

1.	Nguyen, D.T., Gopfert, J.C., Ikezawa, N., Macnevin, G., Kathiresan, M., Conrad, J., Spring, O. and Ro, D.K. Biochemical conservation and evolution of germacrene A oxidase in asteraceae. J. Biol. Chem. 285 (2010) 16588–16598. [DOI] [PMID: 20351109]
2.	Liu, Q., Manzano, D., Tanic, N., Pesic, M., Bankovic, J., Pateraki, I., Ricard, L., Ferrer, A., de Vos, R., van de Krol, S. and Bouwmeester, H. Elucidation and in planta reconstitution of the parthenolide biosynthetic pathway. Metab. Eng. 23 (2014) 145–153. [PMID: 24704560]

[EC 1.14.14.95 created 2011 as EC 1.14.13.123, transferred 2018 to EC 1.14.14.95]

1.14.14.96

Accepted name:

5-O-(4-coumaroyl)-D-quinate 3′-monooxygenase

Reaction:

trans-5-O-(4-coumaroyl)-D-quinate + [reduced NADPH—hemoprotein reductase] + O₂ = trans-5-O-caffeoyl-D-quinate + [oxidized NADPH—hemoprotein reductase] + H₂O

Other name(s):

5-O-(4-coumaroyl)-D-quinate/shikimate 3′-hydroxylase; coumaroylquinate(coumaroylshikimate) 3′-monooxygenase; CYP98A3 (gene name)

Systematic name:

trans-5-O-(4-coumaroyl)-D-quinate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (3′-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein, found in plants. It also acts on trans-5-O-(4-coumaroyl)shikimate.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 112131-08-5

References:

1.	Kühnl, T., Koch, U., Heller, W. and Wellman, E. Chlorogenic acid biosynthesis: characterization of a light-induced microsomal 5-O-(4-coumaroyl)-D-quinate/shikimate 3′-hydroxylase from carrot (Daucus carota L.) cell suspension cultures. Arch. Biochem. Biophys. 258 (1987) 226–232. [DOI] [PMID: 2821918]
2.	Schoch, G., Goepfert, S., Morant, M., Hehn, A., Meyer, D., Ullmann, P. and Werck-Reichhart, D. CYP98A3 from Arabidopsis thaliana is a 3′-hydroxylase of phenolic esters, a missing link in the phenylpropanoid pathway. J. Biol. Chem. 276 (2001) 36566–36574. [PMID: 11429408]
3.	Franke, R., Humphreys, J.M., Hemm, M.R., Denault, J.W., Ruegger, M.O., Cusumano, J.C. and Chapple, C. The Arabidopsis REF8 gene encodes the 3-hydroxylase of phenylpropanoid metabolism. Plant J. 30 (2002) 33–45. [PMID: 11967091]
4.	Matsuno, M., Compagnon, V., Schoch, G.A., Schmitt, M., Debayle, D., Bassard, J.E., Pollet, B., Hehn, A., Heintz, D., Ullmann, P., Lapierre, C., Bernier, F., Ehlting, J. and Werck-Reichhart, D. Evolution of a novel phenolic pathway for pollen development. Science 325 (2009) 1688–1692. [PMID: 19779199]

[EC 1.14.14.96 created 1990 as EC 1.14.13.36, transferred 2018 to EC 1.14.14.96]

1.14.14.97

Accepted name:

methyltetrahydroprotoberberine 14-monooxygenase

Reaction:

(1) (S)-cis-N-methylcanadine + [reduced NADPH—hemoprotein reductase] + O₂ = allocryptopine + [oxidized NADPH—hemoprotein reductase] + H₂O
(2) (S)-cis-N-methylstylopine + [reduced NADPH—hemoprotein reductase] + O₂ = protopine + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of canadine biosynthesis, click here and for diagram of stylopine biosynthesis, click here

Other name(s):

methyltetrahydroprotoberberine 14-hydroxylase; (S)-cis-N-methyltetrahydroberberine 14-monooxygenase; (S)-cis-N-methyltetrahydroprotoberberine-14-hydroxylase; CYP82N4 (gene name); (S)-N-methylcanadine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (14-hydroxylating); (S)-cis-N-methylstylopine 14-hydroxylase

Systematic name:

(S)-cis-N-methylcanadine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (14-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein involved in the biosynthesis of isoquinoline alkaloids in plants. It also hydroxylates (S)-cis-N-methyltetrahydrothalifendine, and (S)-cis-N-methyltetrahydropalmatine.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 113478-42-5

References:

1.	Rueffer, M. and Zenk, M.H. Enzymatic formation of protopines by a microsomal cytochrome-P-450 system of Corydalis vaginans. Tetrahedron Lett. 28 (1987) 5307–5310. [DOI]
2.	Beaudoin, G.A. and Facchini, P.J. Isolation and characterization of a cDNA encoding (S)-cis-N-methylstylopine 14-hydroxylase from opium poppy, a key enzyme in sanguinarine biosynthesis. Biochem. Biophys. Res. Commun. 431 (2013) 597–603. [DOI] [PMID: 23313486]

[EC 1.14.14.97 created 1990 as EC 1.14.13.37, transferred 2018 to EC 1.14.14.97, modified 2023]

1.14.14.98

Accepted name:

protopine 6-monooxygenase

Reaction:

protopine + [reduced NADPH—hemoprotein reductase] + O₂ = 6-hydroxyprotopine + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of stylopine biosynthesis, click here

Other name(s):

protopine 6-hydroxylase; CYP82N2 (gene name)

Systematic name:

protopine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (6-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein involved in benzophenanthridine alkaloid synthesis in higher plants.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 128561-60-4

References:

1.	Tanahashi, T. and Zenk, M.H. Elicitor induction and characterization of microsomal protopine-6-hydroxylase, the central enzyme in benzophenanthridine alkaloid biosynthesis. Phytochemistry 29 (1990) 1113–1122.
2.	Takemura, T., Ikezawa, N., Iwasa, K. and Sato, F. Molecular cloning and characterization of a cytochrome P450 in sanguinarine biosynthesis from Eschscholzia californica cells. Phytochemistry 91 (2013) 100–108. [PMID: 22421633]

[EC 1.14.14.98 created 1999 as EC 1.14.13.55, transferred 2018 to EC 1.14.14.98]

1.14.14.99

Accepted name:

(S)-limonene 3-monooxygenase

Reaction:

(S)-limonene + [reduced NADPH—hemoprotein reductase] + O₂ = (–)-trans-isopiperitenol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of perillyl alcohol, isopiperitol and carveol biosynthesis, click here

Glossary:

limonene = a monoterpenoid
(S)-limonene = (–)-limonene

Other name(s):

(–)-limonene 3-hydroxylase; (–)-limonene 3-monooxygenase; CYP71D15 (gene name)

Systematic name:

(S)-limonene,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (3-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein from peppermint (Mentha piperita).

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, KEGG, CAS registry number: 138066-92-9

References:

1.	Karp, F., Mihaliak, C.A., Harris, J.L. and Croteau, R. Monoterpene biosynthesis: specificity of the hydroxylations of (-)-limonene by enzyme preparations from peppermint (Mentha piperita), spearmint (Mentha spicata), and perilla (Perilla frutescens) leaves. Arch. Biochem. Biophys. 276 (1990) 219–226. [DOI] [PMID: 2297225]
2.	Lupien, S., Karp, F., Wildung, M. and Croteau, R. Regiospecific cytochrome P450 limonene hydroxylases from mint (Mentha) species: cDNA isolation, characterization, and functional expression of (–)-4S-limonene-3-hydroxylase and (–)-4S-limonene-6-hydroxylase. Arch. Biochem. Biophys. 368 (1999) 181–192. [PMID: 10415126]
3.	Wust, M., Little, D.B., Schalk, M. and Croteau, R. Hydroxylation of limonene enantiomers and analogs by recombinant (–)-limonene 3- and 6-hydroxylases from mint (Mentha) species: evidence for catalysis within sterically constrained active sites. Arch. Biochem. Biophys. 387 (2001) 125–136. [PMID: 11368174]

[EC 1.14.14.99 created 1992 as EC 1.14.13.47, modified 2003, transferred 2018 1.14.14.99]

1.14.14.100

Accepted name:

dihydrosanguinarine 10-monooxygenase

Reaction:

dihydrosanguinarine + [reduced NADPH—hemoprotein reductase] + O₂ = 10-hydroxydihydrosanguinarine + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of chelirubine, macarpine and sanguinarine biosynthesis, click here

Other name(s):

dihydrosanguinarine 10-hydroxylase

Systematic name:

dihydrosanguinarine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (10-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein involved in benzophenanthridine alkaloid synthesis in higher plants.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 144388-41-0

References:

1.	De-Eknamkul, W., Tanahashi, T. and Zenk, M.H. Enzymic 10-hydroxylation and 10-O-methylation of dihydrosanguinarine in dihydrochelirubine formation by Eschscholtzia. Phytochemistry 31 (1992) 2713–2717.

[EC 1.14.14.100 created 1999 as EC 1.14.13.56, transferred 2018 to EC 1.14.14.100]

1.14.14.101

Accepted name:

dihydrochelirubine 12-monooxygenase

Reaction:

dihydrochelirubine + [reduced NADPH—hemoprotein reductase] + O₂ = 12-hydroxydihydrochelirubine + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of chelirubine, macarpine and sanguinarine biosynthesis, click here

Other name(s):

dihydrochelirubine 12-hydroxylase

Systematic name:

dihydrochelirubine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (12-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein from the plant Thalictrum bulgaricum.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 158736-41-5

References:

1.	Kammerer, L., De-Eknamkul, W. and Zenk, M.H. Enzymic 12-hydroxylation and 12-O-methylation of dihydrochelirubine in dihydromacarpine formation by Thalictrum bulgaricum. Phytochemistry 36 (1994) 1409–1416.

[EC 1.14.14.101 created 1999 as EC 1.14.13.57, transferred 2018 to EC 1.14.14.101]

1.14.14.102

Accepted name:

N-methylcoclaurine 3′-monooxygenase

Reaction:

(S)-N-methylcoclaurine + [reduced NADPH—hemoprotein reductase] + O₂ = (S)-3′-hydroxy-N-methylcoclaurine + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of reticuline biosynthesis, click here

Other name(s):

N-methylcoclaurine 3′-hydroxylase; CYP80B1 (gene name)

Systematic name:

(S)-N-methylcoclaurine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (3′-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein involved in benzylisoquinoline alkaloid synthesis in higher plants.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 202420-37-9

References:

Pauli, H.H. and Kutchan, T.M. Molecular cloning and functional heterologous expression of two alleles encoding (S)-N-methylcoclaurine 3′-hydroxylase (CYP80B1), a new methyl jasmonate-inducible cytochrome P-450-dependent mono-oxygenase of benzylisoquinoline alkaloid biosynthesis. Plant J. 13 (1998) 793–801. [DOI] [PMID: 9681018]

[EC 1.14.14.102 created 2001 as 1.14.13.71, transferred 2018 to EC 1.14.14.102]

1.14.14.103

Accepted name:

tabersonine 16-hydroxylase

Reaction:

tabersonine + [reduced NADPH—hemoprotein reductase] + O₂ = 16-hydroxytabersonine + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of vindoline biosynthesis, click here

Other name(s):

tabersonine-11-hydroxylase; T11H; CYP71D12 (gene name)

Systematic name:

tabersonine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (16-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein from the plant Madagascar periwinkle (Catharanthus roseus).

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 250378-34-8

References:

St-Pierre, B. and De Luca, V. A cytochrome P-450 monooxygenase catalyzes the first step in the conversion of tabersonine to vindoline in Catharanthus roseus. Plant Physiol. 109 (1995) 131–139. [DOI] [PMID: 12228585]

Besseau, S., Kellner, F., Lanoue, A., Thamm, A.M., Salim, V., Schneider, B., Geu-Flores, F., Hofer, R., Guirimand, G., Guihur, A., Oudin, A., Glevarec, G., Foureau, E., Papon, N., Clastre, M., Giglioli-Guivarc'h, N., St-Pierre, B., Werck-Reichhart, D., Burlat, V., De Luca, V., O'Connor, S.E. and Courdavault, V. A pair of tabersonine 16-hydroxylases initiates the synthesis of vindoline in an organ-dependent manner in Catharanthus roseus. Plant Physiol. 163 (2013) 1792–1803. [PMID: 24108213]

[EC 1.14.14.103 created 2002 as EC 1.14.13.73, transferred 2018 to EC 1.14.14.103]

1.14.14.104

Accepted name:

vinorine hydroxylase

Reaction:

vinorine + [reduced NADPH—hemoprotein reductase] + O₂ = vomilenine + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of ajmaline, vinorine, vomilenine and raucaffricine biosynthesis, click here

Systematic name:

vinorine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (21α-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein from the plant Rauvolfia serpentina. Forms a stage in the biosynthesis of the indole alkaloid ajmaline.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 162875-03-8

References:

1.	Falkenhagen, H. and Stöckligt, J. Enzymatic biosynthesis of vomilenine, a key intermediate of the ajmaline pathway, catalysed by a novel cytochrome P-450-dependent enzyme from plant cell cultures of Rauwolfia serpentina. Z. Naturforsch. C: Biosci. 50 (1995) 45–53.

[EC 1.14.14.104 created 2002 as EC 1.14.13.75, transferred 2018 to EC 1.14.14.104]

1.14.14.105

Accepted name:

taxane 10β-hydroxylase

Reaction:

taxa-4(20),11-dien-5α-yl acetate + [reduced NADPH—hemoprotein reductase] + O₂ = 10β-hydroxytaxa-4(20),11-dien-5α-yl acetate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of taxadiene hydroxylation, click here

Other name(s):

CYP725A1 (gene name); 5-α-taxadienol-10-β-hydroxylase

Systematic name:

taxa-4(20),11-dien-5α-yl acetate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (10β-hydroxylating)

Comments:

This microsomal cytochrome-P-450 (heme-thiolate) enzyme from the plant Taxus cuspidata is involved in the biosynthesis of the diterpenoid antineoplastic drug taxol (paclitaxel).

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 337514-75-7

References:

1.	Wheeler, A.L., Long, R.M., Ketchum, R.E., Rithner, C.D., Williams, R.M. and Croteau, R. Taxol biosynthesis: differential transformations of taxadien-5α-ol and its acetate ester by cytochrome P₄₅₀ hydroxylases from Taxus suspension cells. Arch. Biochem. Biophys. 390 (2001) 265. [DOI] [PMID: 11396929]
2.	Jennewein, S., Rithner, C.D., Williams, R.M. and Croteau, R.B. Taxol biosynthesis: taxane 13 α-hydroxylase is a cytochrome P₄₅₀-dependent monooxygenase. Proc. Natl. Acad. Sci. USA 98 (2001) 13595. [DOI] [PMID: 11707604]
3.	Schoendorf, A., Rithner, C.D., Williams, R.M. and Croteau, R.B. Molecular cloning of a cytochrome P₄₅₀ taxane 10β-hydroxylase cDNA from Taxus and functional expression in yeast. Proc. Natl. Acad. Sci. USA 98 (2001) 1501–1506. [DOI] [PMID: 11171980]

[EC 1.14.14.105 created 2002 as EC 1.14.13.76, transferred 2018 to EC 1.14.14.105]

1.14.14.106

Accepted name:

taxane 13α-hydroxylase

Reaction:

taxa-4(20),11-dien-5α-ol + [reduced NADPH—hemoprotein reductase] + O₂ = taxa-4(20),11-dien-5α,13α-diol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of taxadiene hydroxylation, click here

Other name(s):

CYP725A2 (gene name)

Systematic name:

taxa-4(20),11-dien-5α-ol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (13α-hydroxylating)

Comments:

This cytochrome-P-450(heme-thiolate) enzyme from the plant Taxus cuspidata is involved in the biosynthesis of the diterpenoid antineoplastic drug taxol (paclitaxel).

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 399030-58-1

References:

1.	Wheeler, A.L., Long, R.M., Ketchum, R.E., Rithner, C.D., Williams, R.M. and Croteau, R. Taxol biosynthesis: differential transformations of taxadien-5α-ol and its acetate ester by cytochrome P₄₅₀ hydroxylases from Taxus suspension cells. Arch. Biochem. Biophys. 390 (2001) 265. [DOI] [PMID: 11396929]
2.	Jennewein, S., Rithner, C.D., Williams, R.M. and Croteau, R.B. Taxol biosynthesis: taxane 13 α-hydroxylase is a cytochrome P₄₅₀-dependent monooxygenase. Proc. Natl. Acad. Sci. USA 98 (2001) 13595. [DOI] [PMID: 11707604]

[EC 1.14.14.106 created 2002 as EC 1.14.13.77, transferred 2018 to EC 1.14.14.106]

1.14.14.107

Accepted name:

ent-kaurenoic acid monooxygenase

Reaction:

ent-kaur-16-en-19-oate + 3 [reduced NADPH—hemoprotein reductase] + 3 O₂ = gibberellin A₁₂ + 3 [oxidized NADPH—hemoprotein reductase] + 4 H₂O (overall reaction)
(1a) ent-kaur-16-en-19-oate + [reduced NADPH—hemoprotein reductase] + O₂ = ent-7α-hydroxykaur-16-en-19-oate + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) ent-7α-hydroxykaur-16-en-19-oate + [reduced NADPH—hemoprotein reductase] + O₂ = gibberellin A₁₂ aldehyde + [oxidized NADPH—hemoprotein reductase] + 2 H₂O
(1c) gibberellin A₁₂ aldehyde + [reduced NADPH—hemoprotein reductase] + O₂ = gibberellin A₁₂ + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of gibberellin A₁₂ biosynthesis, click here

Other name(s):

KAO1 (gene name); CYP88A3 (gene name); ent-kaurenoic acid oxidase

Systematic name:

ent-kaur-16-en-19-oate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein from plants. Catalyses three sucessive oxidations of ent-kaurenoic acid. The second step includes a ring-B contraction giving the gibbane skeleton. In pumpkin (Cucurbita maxima) ent-6α,7α-dihydroxykaur-16-en-19-oate is also formed.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 337507-95-6

References:

1.	Helliwell, C.A., Chandler, P.M., Poole, A., Dennis, E.S. and Peacock, W.J. The CYP88A cytochrome P450, ent-kaurenoic acid oxidase, catalyzes three steps of the gibberellin biosynthesis pathway. Proc. Natl. Acad. Sci. USA 98 (2001) 2065–2070. [DOI] [PMID: 11172076]

[EC 1.14.14.107 created 2002 as EC 1.14.13.79, transferred 2018 to EC 1.14.14.107]

1.14.14.108

Accepted name:

2,5-diketocamphane 1,2-monooxygenase

Reaction:

(+)-bornane-2,5-dione + FMNH₂ + O₂ = (+)-5-oxo-1,2-campholide + FMN + H₂O

For diagram of camphor catabolism, click here

Glossary:

(+)-bornane-2,5-dione = 2,5-diketocamphane

Other name(s):

2,5-diketocamphane lactonizing enzyme; ketolactonase I (ambiguous); 2,5-diketocamphane 1,2-monooxygenase oxygenating component; 2,5-DKCMO; camP (gene name); camphor 1,2-monooxygenase; camphor ketolactonase I

Systematic name:

(+)-bornane-2,5-dione,FMNH₂:oxygen oxidoreductase (1,2-lactonizing)

Comments:

A Baeyer-Villiger monooxygenase isolated from camphor-grown strains of Pseudomonas putida and encoded on the cam plasmid. Involved in the degradation of (+)-camphor. Requires a dedicated NADH-FMN reductase [cf. EC 1.5.1.42, FMN reductase (NADH)] [1-3]. Can accept several bicyclic ketones including (+)- and (–)-camphor [6] and adamantanone [4]. The product spontaneously converts to [(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetate.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, KEGG

References:

1.	Conrad, H.E., DuBus, R., Namtvedt, M.J. and Gunsalus, I.C. Mixed function oxidation. II. Separation and properties of the enzymes catalyzing camphor lactonizaton. J. Biol. Chem. 240 (1965) 495–503. [PMID: 14253460]
2.	Yu, C.A. and Gunsalus, I.C. Monoxygenases. VII. Camphor ketolactonase I and the role of three protein components. J. Biol. Chem. 244 (1969) 6149–6152. [PMID: 4310834]
3.	Taylor, D.G. and Trudgill, P.W. Camphor revisited: studies of 2,5-diketocamphane 1,2-monooxygenase from Pseudomonas putida ATCC 17453. J. Bacteriol. 165 (1986) 489–497. [DOI] [PMID: 3944058]
4.	Selifonov, S.A. Microbial oxidation of adamantanone by Pseudomonas putida carrying the camphor catabolic plasmid. Biochem. Biophys. Res. Commun. 186 (1992) 1429–1436. [DOI] [PMID: 1510672]
5.	Jones, K.H., Smith, R.T. and Trudgill, P.W. Diketocamphane enantiomer-specific ’Baeyer-Villiger’ monooxygenases from camphor-grown Pseudomonas putida ATCC 17453. J. Gen. Microbiol. 139 (1993) 797–805. [DOI] [PMID: 8515237]
6.	Kadow, M., Sass, S., Schmidt, M. and Bornscheuer, U.T. Recombinant expression and purification of the 2,5-diketocamphane 1,2-monooxygenase from the camphor metabolizing Pseudomonas putida strain NCIMB 10007. AMB Express 1:13 (2011). [DOI] [PMID: 21906366]
7.	Iwaki, H., Grosse, S., Bergeron, H., Leisch, H., Morley, K., Hasegawa, Y. and Lau, P.C. Camphor pathway redux: functional recombinant expression of 2,5- and 3,6-diketocamphane monooxygenases of Pseudomonas putida ATCC 17453 with their cognate flavin reductase catalyzing Baeyer-Villiger reactions. Appl. Environ. Microbiol. 79 (2013) 3282–3293. [PMID: 23524667]

[EC 1.14.14.108 created 1972 as EC 1.14.15.2, transferred 2012 to EC 1.14.13.162, transferred 2018 to EC 1.14.14.108]

1.14.14.109

Accepted name:

3-hydroxyindolin-2-one monooxygenase

Reaction:

3-hydroxyindolin-2-one + [reduced NADPH—hemoprotein reductase] + O₂ = 2-hydroxy-2H-1,4-benzoxazin-3(4H)-one [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of benzoxazinone biosynthesis, click here

Glossary:

2-hydroxy-2H-1,4-benzoxazin-3(4H)-one = HBOA

Other name(s):

BX4 (gene name); CYP71C1 (gene name)

Systematic name:

3-hydroxyindolin-2-one,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (2-hydroxy-2H-1,4-benzoxazin-3(4H)-one-forming)

Comments:

A cytochrome P-450 (heme-thiolate) protein. The enzyme is involved in the biosynthesis of protective and allelophatic benzoxazinoids in some plants, most commonly from the family of Poaceae (grasses).

Links to other databases:

References:

1.	Glawischnig, E., Grun, S., Frey, M. and Gierl, A. Cytochrome P450 monooxygenases of DIBOA biosynthesis: specificity and conservation among grasses. Phytochemistry 50 (1999) 925–930. [DOI] [PMID: 10385992]
2.	Frey, M., Chomet, P., Glawischnig, E., Stettner, C., Grün, S., Winklmair, A., Eisenreich, W., Bacher, A., Meeley, R.B., Briggs, S.P., Simcox, K. and Gierl, A. Analysis of a chemical plant defense mechanism in grasses. Science 277 (1997) 696–699. [DOI] [PMID: 9235894]
3.	Spiteller, P., Glawischnig, E., Gierl, A. and Steglich, W. Studies on the biosynthesis of 2-hydroxy-1,4-benzoxazin-3-one (HBOA) from 3-hydroxyindolin-2-one in Zea mays. Phytochemistry 57 (2001) 373–376. [DOI] [PMID: 11393516]

[EC 1.14.14.109 created 2012 as EC 1.14.13.139, transferred 2018 to EC 1.14.14.109]

1.14.14.110

Accepted name:

2-hydroxy-1,4-benzoxazin-3-one monooxygenase

Reaction:

2-hydroxy-2H-1,4-benzoxazin-3(4H)-one + [reduced NADPH—hemoprotein reductase] + O₂ = 2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of benzoxazinone biosynthesis, click here

Glossary:

2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one = DIBOA
2-hydroxy-2H-1,4-benzoxazin-3(4H)-one = HBOA

Other name(s):

BX5 (gene name); CYP71C3 (gene name)

Systematic name:

2-hydroxy-2H-1,4-benzoxazin-3(4H)-one,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (N-hydroxylating)

Comments:

Links to other databases:

References:

1.	Bailey, B.A. and Larson, R.L. Maize microsomal benzoxazinone N-monooxygenase. Plant Physiol. 95 (1991) 792–796. [PMID: 16668055]
2.	Glawischnig, E., Grun, S., Frey, M. and Gierl, A. Cytochrome P450 monooxygenases of DIBOA biosynthesis: specificity and conservation among grasses. Phytochemistry 50 (1999) 925–930. [DOI] [PMID: 10385992]

[EC 1.14.14.110 created 2012 as EC 1.14.13.140, transferred 2018 to EC 1.14.14.110]

1.14.14.111

Accepted name:

9β-pimara-7,15-diene oxidase

Reaction:

9β-pimara-7,15-diene + 3 O₂ + 3 [reduced NADPH—hemoprotein reductase] = 9β-pimara-7,15-dien-19-oate + 3 [oxidized NADPH—hemoprotein reductase] + 4 H₂O (overall reaction)
(1a) 9β-pimara-7,15-diene + O₂ + [reduced NADPH—hemoprotein reductase] = 9β-pimara-7,15-dien-19-ol + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) 9β-pimara-7,15-dien-19-ol + O₂ + [reduced NADPH—hemoprotein reductase] = 9β-pimara-7,15-dien-19-al + [oxidized NADPH—hemoprotein reductase] + 2 H₂O
(1c) 9β-pimara-7,15-dien-19-al + O₂ + [reduced NADPH—hemoprotein reductase] = 9β-pimara-7,15-dien-19-oate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of momilactone A biosynthesis, click here

Glossary:

syn-pimara-7,15-diene = 9β-pimara-7,15-diene

Other name(s):

CYP99A3; 9β-pimara-7,15-diene monooxygenase

Systematic name:

9β-pimara-7,15-diene,[reduced NADPH—hemoprotein reductase]:oxygen 19-oxidoreductase

Comments:

A cytochrome P-450 (heme-thiolate) protein. The enzyme from rice (Oryza sativa) is involved in the biosynthesis of the phytoalexin momilactone. It also acts similarly on 9β-stemod-13(17)-ene.

Links to other databases:

References:

1.	Wang, Q., Hillwig, M.L. and Peters, R.J. CYP99A3: functional identification of a diterpene oxidase from the momilactone biosynthetic gene cluster in rice. Plant J. 65 (2011) 87–95. [DOI] [PMID: 21175892]

[EC 1.14.14.111 created 2012 as EC 1.14.13.144, transferred 2018 to EC 1.14.14.111]

1.14.14.112

Accepted name:

ent-cassa-12,15-diene 11-hydroxylase

Reaction:

ent-cassa-12,15-diene + O₂ + [reduced NADPH—hemoprotein reductase] = ent-11β-hydroxycassa-12,15-diene + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of biosynthesis of diterpenoids from ent-copalyl diphosphate, click here

Other name(s):

ent-cassadiene C11α-hydroxylase; CYP76M7

Systematic name:

ent-cassa-12,15-diene,[reduced NADPH—hemoprotein reductase]:oxygen 11-oxidoreductase

Comments:

A cytochrome P-450 (heme-thiolate) protein. The enzyme from rice (Oryza sativa) is involved in the biosynthesis of the antifungal phytocassanes.

Links to other databases:

References:

1.	Swaminathan, S., Morrone, D., Wang, Q., Fulton, D.B. and Peters, R.J. CYP76M7 is an ent-cassadiene C11α-hydroxylase defining a second multifunctional diterpenoid biosynthetic gene cluster in rice. Plant Cell 21 (2009) 3315–3325. [DOI] [PMID: 19825834]

[EC 1.14.14.112 created 2012 as EC 1.14.13.145, transferred 2018 to EC 1.14.14.112]

1.14.14.113

Accepted name:

α-humulene 10-hydroxylase

Reaction:

α-humulene + O₂ + [reduced NADPH—hemoprotein reductase] = 10-hydroxy-α-humulene + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of zerumbone biosynthesis, click here

Other name(s):

CYP71BA1

Systematic name:

α-humulene,[reduced NADPH—hemoprotein reductase]:oxygen 10-oxidoreductase

Comments:

A cytochrome P-450 (heme-thiolate) protein. The recommended numbering of humulene gives 10-hydroxy-α-humulene as the product rather than 8-hydroxy-α-humulene as used by the reference. See Section F: Natural Product Nomenclature.

Links to other databases:

References:

1.	Yu, F., Okamoto, S., Harada, H., Yamasaki, K., Misawa, N. and Utsumi, R. Zingiber zerumbet CYP71BA1 catalyzes the conversion of α-humulene to 8-hydroxy-α-humulene in zerumbone biosynthesis. Cell. Mol. Life Sci. 68 (2011) 1033–1040. [DOI] [PMID: 20730551]

[EC 1.14.14.113 created 2012 as EC 1.14.13.150, transferred 2018 to EC 1.14.14.113]

1.14.14.114

Accepted name:

amorpha-4,11-diene 12-monooxygenase

Reaction:

amorpha-4,11-diene + 3 O₂ + 3 [reduced NADPH—hemoprotein reductase] = artemisinate + 3 [oxidized NADPH—hemoprotein reductase] + 4 H₂O (overall reaction)
(1a) amorpha-4,11-diene + O₂ + [reduced NADPH—hemoprotein reductase] = artemisinic alcohol + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) artemisinic alcohol + O₂ + [reduced NADPH—hemoprotein reductase] = artemisinic aldehyde + [oxidized NADPH—hemoprotein reductase] + 2 H₂O
(1c) artemisinic aldehyde + O₂ + [reduced NADPH—hemoprotein reductase] = artemisinate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of artemisinin biosynthesis, click here

Other name(s):

CYP71AV1

Systematic name:

amorpha-4,11-diene,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (12-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. Cloned from the plant Artemisia annua (sweet wormwood). Part of the biosynthetic pathway of artemisinin.

Links to other databases:

References:

Teoh, K.H., Polichuk, D.R., Reed, D.W., Nowak, G. and Covello, P.S. Artemisia annua L. (Asteraceae) trichome-specific cDNAs reveal CYP71AV1, a cytochrome P450 with a key role in the biosynthesis of the antimalarial sesquiterpene lactone artemisinin. FEBS Lett. 580 (2006) 1411–1416. [DOI] [PMID: 16458889]

[EC 1.14.14.114 created 2012 as EC 1.14.13.158, transferred 2018 to EC 1.14.14.114]

1.14.14.115

Accepted name:

11-oxo-β-amyrin 30-oxidase

Reaction:

11-oxo-β-amyrin + 3 O₂ + 3 [reduced NADPH—hemoprotein reductase] = glycyrrhetinate + 3 [oxidized NADPH—hemoprotein reductase] + 4 H₂O (overall reaction)
(1a) 11-oxo-β-amyrin + O₂ + [reduced NADPH—hemoprotein reductase] = 30-hydroxy-11-oxo-β-amyrin + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) 30-hydroxy-11-oxo-β-amyrin + O₂ + [reduced NADPH—hemoprotein reductase] = glycyrrhetaldehyde + [oxidized NADPH—hemoprotein reductase] + 2 H₂O
(1c) glycyrrhetaldehyde + O₂ + [reduced NADPH—hemoprotein reductase] = glycyrrhetinate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of glycyrrhenate biosynthesis, click here

Other name(s):

CYP72A; CYP72A154; 11-oxo-β-amyrin 30-monooxygenase

Systematic name:

11-oxo-β-amyrin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (30-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. The enzyme from the plant Glycyrrhiza uralensis (licorice) is involved in the biosynthesis of the triterpenoid saponin glycyrrhizin. The enzyme from the plant Medicago truncatula can also hydroxylate β-amyrin.

Links to other databases:

References:

Seki, H., Sawai, S., Ohyama, K., Mizutani, M., Ohnishi, T., Sudo, H., Fukushima, E.O., Akashi, T., Aoki, T., Saito, K. and Muranaka, T. Triterpene functional genomics in licorice for identification of CYP72A154 involved in the biosynthesis of glycyrrhizin. Plant Cell 23 (2011) 4112–4123. [DOI] [PMID: 22128119]

[EC 1.14.14.115 created 2013 as EC 1.14.13.173, transferred 2018 to EC 1.14.14.115]

1.14.14.116

Accepted name:

averantin hydroxylase

Reaction:

(1) (1′S)-averantin + [reduced NADPH—hemoprotein reductase] + O₂ = (1′S,5′S)-5′-hydroxyaverantin + [oxidized NADPH—hemoprotein reductase] + H₂O
(2) (1′S)-averantin + [reduced NADPH—hemoprotein reductase] + O₂ = (1′S,5′R)-5′-hydroxyaverantin + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of aflatoxin biosynthesis (part 1), click here

Glossary:

averantin = 1,3,6,8-tetrahydroxy-2-[(1S)-1-hydroxyhexyl]anthracene-9,10-dione

Other name(s):

AVN hydroxylase; avnA (gene name); CYP60A1

Systematic name:

(1′S)-averantin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (5′-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein isolated from the saprophytic mold Aspergillus parasiticus. Involved in aflatoxin biosynthesis. Does not react with (1′R)-averantin.

Links to other databases:

References:

1.	Yabe, K., Matsuyama, Y., Ando, Y., Nakajima, H. and Hamasaki, T. Stereochemistry during aflatoxin biosynthesis: conversion of norsolorinic acid to averufin. Appl. Environ. Microbiol. 59 (1993) 2486–2492. [PMID: 8368836]
2.	Yu, J., Chang, P.K., Cary, J.W., Bhatnagar, D. and Cleveland, T.E. avnA, a gene encoding a cytochrome P-450 monooxygenase, is involved in the conversion of averantin to averufin in aflatoxin biosynthesis in Aspergillus parasiticus. Appl. Environ. Microbiol. 63 (1997) 1349–1356. [PMID: 9097431]

[EC 1.14.14.116 created 2013 as EC 1.14.13.174, transferred 2018 to EC 1.14.14.116]

1.14.14.117

Accepted name:

aflatoxin B synthase

Reaction:

(1) 8-O-methylsterigmatocystin + 2 [reduced NADPH—hemoprotein reductase] + 2 O₂ = aflatoxin B₁ + 2 [oxidized NADPH—hemoprotein reductase] + H₂O + methanol + CO₂
(2) 8-O-methyldihydrosterigmatocystin + 2 [reduced NADPH—hemoprotein reductase] + 2 O₂ = aflatoxin B₂ + 2 [oxidized NADPH—hemoprotein reductase] + H₂O + methanol + CO₂

For diagram of aflatoxin biosynthesis (part 4), click here

Glossary:

aflatoxin B₁ = (6aR,9aS)-4-methoxy-2,3,6a,9a-tetrahydrocyclopenta[c]furo[3′,2′:4,5]furo[2,3-h][1]benzopyran-1,11-dione
aflatoxin B₂ = (6aR,9aS)-4-methoxy-2,3,6a,8,9,9a-hexahydrocyclopenta[c]furo[3′,2′:4,5]furo[2,3-h][1]benzopyran-1,11-dione
8-O-methylsterigmatocystin = 6,8-dimethoxy-3a,12c-dihydrofuro[3′,2′:4,5]furo[2,3-c]xanthen-7-one
8-O-methyldihydrosterigmatocystin = 6,8-dimethoxy-1,2,3a,12c-tetrahydrofuro[3′,2′:4,5]furo[2,3-c]xanthen-7-one

Other name(s):

ordA (gene name)

Systematic name:

8-O-methylsterigmatocystin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (aflatoxin-B-forming)

Comments:

A cytochrome P-450 (heme-thiolate) protein. Isolated from the mold Aspergillus parasiticus.

Links to other databases:

References:

1.	Bhatnagar, D., Cleveland, T.E. and Kingston, D.G. Enzymological evidence for separate pathways for aflatoxin B₁ and B₂ biosynthesis. Biochemistry 30 (1991) 4343–4350. [PMID: 1902378]
2.	Yu, J., Chang, P.K., Ehrlich, K.C., Cary, J.W., Montalbano, B., Dyer, J.M., Bhatnagar, D. and Cleveland, T.E. Characterization of the critical amino acids of an Aspergillus parasiticus cytochrome P-450 monooxygenase encoded by ordA that is involved in the biosynthesis of aflatoxins B1, G1, B2, and G2. Appl. Environ. Microbiol. 64 (1998) 4834–4841. [PMID: 9835571]
3.	Udwary, D.W., Casillas, L. K. and Townsend, C.A. Synthesis of 11-hydroxyl O-methylsterigmatocystin and the role of a cytochrome P-450 in the final step of aflatoxin biosynthesis. J. Am. Chem. Soc. 124 (2002) 5294–5303. [DOI] [PMID: 11996570]

[EC 1.14.14.117 created 2013 as EC 1.14.13.175, transferred 2018 to EC 1.14.14.117]

1.14.14.118

Accepted name:

tryprostatin B 6-hydroxylase

Reaction:

tryprostatin B + [reduced NADPH—hemoprotein reductase] + O₂ = 6-hydroxytryprostatin B + [oxidized NADPH—hemoprotein reductase] + H₂O

Glossary:

tryprostatin B = (3S,8aS)-3-{[2-(3-methylbut-2-en-1-yl)-1H-indol-3-yl]methyl}hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
6-hydroxytryprostatin B = (3S,8aS)-3-{[6-hydroxy-2-(3-methylbut-2-en-1-yl)-1H-indol-3-yl]methyl}hexahydropyrrolo[1,2-a]pyrazine-1,4-dione

Other name(s):

ftmC (gene name)

Systematic name:

tryprostatin B,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (6-hydroxytryprostatin B-forming)

Comments:

A cytochrome P-450 (heme-thiolate) protein. Involved in the biosynthetic pathways of several indole alkaloids such as tryprostatins, fumitremorgins and verruculogen.

Links to other databases:

References:

1.	Kato, N., Suzuki, H., Takagi, H., Asami, Y., Kakeya, H., Uramoto, M., Usui, T., Takahashi, S., Sugimoto, Y. and Osada, H. Identification of cytochrome P450s required for fumitremorgin biosynthesis in Aspergillus fumigatus. ChemBioChem 10 (2009) 920–928. [DOI] [PMID: 19226505]

[EC 1.14.14.118 created 2013 as EC 1.14.13.176, transferred 2018 to EC 1.14.14.118]

1.14.14.119

Accepted name:

fumitremorgin C monooxygenase

Reaction:

fumitremorgin C + 2 [reduced NADPH—hemoprotein reductase] + 2 O₂ = 12α,13α-dihydroxyfumitremorgin C + 2 [oxidized NADPH—hemoprotein reductase] + 2 H₂O

For diagram of fumitremorgin alkaloid biosynthesis (part 2), click here

Glossary:

fumitremorgin C = (5aS,12S,14aS)-9-methoxy-12-(2-methylprop-1-en-1-yl)-1,2,3,5a,6,11,12,14a-octahydro-5H,14H-pyrrolo[1′′,2′′:4′,5′]pyrazino[1′,2′:1,6]pyrido[3,4-b]indole-5,14-dione
12α,13α-dihydroxyfumitremorgin = (5aR,6S,12S,14aS)-5a,6-dihydroxy-9-methoxy-12-(2-methylprop-1-en-1-yl)-1,2,3,5a,6,11,12,14a-octahydro-5H,14H-pyrrolo[1′′,2′′:4′,5′]pyrazino[1′,2′:1,6]pyrido[3,4-b]indole-5,14-dione

Other name(s):

ftmG (gene name)

Systematic name:

fumitremorgin C,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (12α,13α-dihydroxyfumitremorgin C-forming)

Comments:

A cytochrome P-450 (heme-thiolate) protein. Involved in the biosynthetic pathway of the indole alkaloid verruculogen.

Links to other databases:

References:

1.	Kato, N., Suzuki, H., Takagi, H., Asami, Y., Kakeya, H., Uramoto, M., Usui, T., Takahashi, S., Sugimoto, Y. and Osada, H. Identification of cytochrome P450s required for fumitremorgin biosynthesis in Aspergillus fumigatus. ChemBioChem 10 (2009) 920–928. [DOI] [PMID: 19226505]

[EC 1.14.14.119 created 2013 as EC 1.14.13.177, transferred 2018 to EC 1.14.14.119]

1.14.14.120

Accepted name:

dammarenediol 12-hydroxylase

Reaction:

dammarenediol-II + [reduced NADPH—hemoprotein reductase] + O₂ = protopanaxadiol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of dammarenediol II and tirucalla-7,24-dien-3β-ol biosynthesis, click here

Glossary:

dammarenediol-II = dammar-24-ene-3β,20-diol
protopanaxadiol = dammar-24-ene-3β,12β,20-triol

Other name(s):

protopanaxadiol synthase; CYP716A47

Systematic name:

dammarenediol-II,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (12β-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein isolated from ginseng (Panax ginseng). Involved in the biosynthetic pathway of ginsenosides.

Links to other databases:

References:

1.	Han, J.Y., Kim, H.J., Kwon, Y.S. and Choi, Y.E. The Cyt P450 enzyme CYP716A47 catalyzes the formation of protopanaxadiol from dammarenediol-II during ginsenoside biosynthesis in Panax ginseng. Plant Cell Physiol. 52 (2011) 2062–2073. [DOI] [PMID: 22039120]

[EC 1.14.14.120 created 2013 as EC 1.14.13.183, transferred 2018 to EC 1.14.14.120]

1.14.14.121

Accepted name:

protopanaxadiol 6-hydroxylase

Reaction:

protopanaxadiol + [reduced NADPH—hemoprotein reductase] + O₂ = protopanaxatriol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of dammarenediol II and tirucalla-7,24-dien-3β-ol biosynthesis, click here

Glossary:

protopanaxadiol = dammar-24-ene-3β,12β,20-triol
protopanaxatriol = dammar-24-ene-3β,6α,12β,20-tetrol

Other name(s):

protopanaxatriol synthase; P6H; CYP716A53v2

Systematic name:

protopanaxadiol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (6α-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein isolated from the rhizomes of ginseng (Panax ginseng). Involved in the biosynthetic pathway of ginsenosides.

Links to other databases:

References:

1.	Yue, C.J., Zhou, X. and Zhong, J.J. Protopanaxadiol 6-hydroxylase and its role in regulating the ginsenoside heterogeneity in Panax notoginseng cells. Biotechnol. Bioeng. 100 (2008) 933–940. [DOI] [PMID: 18351680]
2.	Han, J.Y., Hwang, H.S., Choi, S.W., Kim, H.J. and Choi, Y.E. Cytochrome P450 CYP716A53v2 catalyzes the formation of protopanaxatriol from protopanaxadiol during ginsenoside biosynthesis in Panax ginseng. Plant Cell Physiol. 53 (2012) 1535–1545. [DOI] [PMID: 22875608]

[EC 1.14.14.121 created 2013 as EC 1.14.13.184, transferred 2018 to EC 1.14.14.121]

1.14.14.122

Accepted name:

oryzalexin E synthase

Reaction:

ent-sandaracopimaradien-3β-ol + [reduced NADPH—hemoprotein reductase] + O₂ = oryzalexin E + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of oryzalexins biosynthesis, click here

Glossary:

oryzalexin E = ent-sandaracopimaradiene-3β,9α-diol = (3R,4aR,4bS,7S,10aR)-7-ethenyl-1,1,4a,7-tetramethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthren-2,4b-diol
ent-sandaracopimaradien-3β-ol = (3R,4aR,4bR,7S,10aS)-7-ethenyl-1,1,4a,7-tetramethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthren-2-ol

Other name(s):

CYP76M6

Systematic name:

ent-sandaracopimaradien-3β-ol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (oryzalexin-E-forming)

Comments:

A cytochrome P-450 (heme-thiolate) protein. Isolated from Oryza sativa (rice). Oryzalexin E is a phytoalexin.

Links to other databases:

References:

1.	Wu, Y., Wang, Q., Hillwig, M.L. and Peters, R.J. Picking sides: distinct roles for CYP76M6 and CYP76M8 in rice oryzalexin biosynthesis. Biochem. J. 454 (2013) 209–216. [DOI] [PMID: 23795884]

[EC 1.14.14.122 created 2014 as EC 1.14.13.192, transferred 2018 to EC 1.14.14.122]

1.14.14.123

Accepted name:

oryzalexin D synthase

Reaction:

ent-sandaracopimaradien-3β-ol + [reduced NADPH—hemoprotein reductase] + O₂ = oryzalexin D + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of oryzalexins biosynthesis, click here

Glossary:

oryzalexin D = ent-sandaracopimaradiene-3β,7α-diol = (3R,4aR,4bS,7S,9S,10aS)-7-ethenyl-1,1,4a,7-tetramethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthren-2,9-diol
ent-sandaracopimaradien-3β-ol = (3R,4aR,4bR,7S,10aS)-7-ethenyl-1,1,4a,7-tetramethyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthren-2-ol

Other name(s):

CYP76M8

Systematic name:

ent-sandaracopimaradien-3β-ol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (oryzalexin-D-forming)

Comments:

A cytochrome P-450 (heme-thiolate) protein. Isolated from Oryza sativa (rice). Oryzalexin D is a phytoalexin.

Links to other databases:

References:

1.	Wu, Y., Wang, Q., Hillwig, M.L. and Peters, R.J. Picking sides: distinct roles for CYP76M6 and CYP76M8 in rice oryzalexin biosynthesis. Biochem. J. 454 (2013) 209–216. [DOI] [PMID: 23795884]

[EC 1.14.14.123 created 2014 as EC 1.14.13.193, transferred 2018 to EC 1.14.14.123]

1.14.14.124

Accepted name:

dihydromonacolin L hydroxylase

Reaction:

dihydromonacolin L acid + O₂ + [reduced NADPH—hemoprotein reductase] = monacolin L acid + [oxidized NADPH—hemoprotein reductase] + 2 H₂O (overall reaction)
(1a) dihydromonacolin L acid + O₂ + [reduced NADPH—hemoprotein reductase] = 3α-hydroxy-3,5-dihydromonacolin L acid + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) 3α-hydroxy-3,5-dihydromonacolin L acid = monacolin L acid + H₂O (spontaneous)

For diagram of lovastatin biosynthesis, click here

Glossary:

dihydromonacolin L acid = (3R,5R)-7-[(1S,2S,4aR,6R,8aS)-2,6-dimethyl-1,2,4a,5,6,7,8,8a-octahydronaphthalen1yl]-3,5-dihydroxyheptanoate
monacolin L acid = (3R,5R)-7-[(1S,2S,6R,8aR)-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoate
3α-hydroxy-3,5-dihydromonacolin L = (3R,5R)-7-[(1R,2R,3S,6R,8aR)-3-hydroxy-2,6-dimethyl-1,2,3,5,6,7,8,8a-octahydronaphthalen-1-yl]-3,5-dihydroxyheptanoate

Other name(s):

LovA (ambiguous)

Systematic name:

dihydromonacolin L acid,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (3-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. The dehydration of 3α-hydroxy-3,5-dihydromonacolin L acid is believed to be spontaneous [1,2]. The enzyme from fungi also catalyses the reaction of EC 1.14.14.125, monacolin L hydroxylase [3].

Links to other databases:

References:

1.	Treiber, L.R., Reamer, R.A., Rooney, C.S. and Ramjit, H.G. Origin of monacolin L from Aspergillus terreus cultures. J. Antibiot. (Tokyo) 42 (1989) 30–36. [PMID: 2921224]
2.	Nakamura, T., Komagata, D., Murakawa, S., Sakai, K. and Endo, A. Isolation and biosynthesis of 3α-hydroxy-3,5-dihydromonacolin L. J. Antibiot. (Tokyo) 43 (1990) 1597–1600. [PMID: 2276977]
3.	Barriuso, J., Nguyen, D.T., Li, J.W., Roberts, J.N., MacNevin, G., Chaytor, J.L., Marcus, S.L., Vederas, J.C. and Ro, D.K. Double oxidation of the cyclic nonaketide dihydromonacolin L to monacolin J by a single cytochrome P450 monooxygenase, LovA. J. Am. Chem. Soc. 133 (2011) 8078–8081. [DOI] [PMID: 21495633]

[EC 1.14.14.124 created 2014 as EC 1.14.13.197, transferred 2018 to EC 1.14.14.124]

1.14.14.125

Accepted name:

monacolin L hydroxylase

Reaction:

monacolin L acid + O₂ + [reduced NADPH—hemoprotein reductase] = monacolin J acid + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of lovastatin biosynthesis, click here

Glossary:

monacolin L acid = (3R,5R)-7-[(1S,2S,6R,8aR)-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid
monacolin J acid = (3R,5R)-7-[(1S,2S,6R,8S,8aR)-8-hydroxy-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid

Other name(s):

LovA (ambiguous)

Systematic name:

monacolin L acid,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (8-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. The enzyme from fungi also catalyses the reaction of EC 1.14.14.124, dihydromonacolin L hydroxylase.

Links to other databases:

References:

Barriuso, J., Nguyen, D.T., Li, J.W., Roberts, J.N., MacNevin, G., Chaytor, J.L., Marcus, S.L., Vederas, J.C. and Ro, D.K. Double oxidation of the cyclic nonaketide dihydromonacolin L to monacolin J by a single cytochrome P450 monooxygenase, LovA. J. Am. Chem. Soc. 133 (2011) 8078–8081. [DOI] [PMID: 21495633]

[EC 1.14.14.125 created 2014 as EC 1.14.13.198, transferred 2018 to EC 1.14.14.125]

1.14.14.126

Accepted name:

β-amyrin 28-monooxygenase

Reaction:

β-amyrin + 3 O₂ + 3 [reduced NADPH—hemoprotein reductase] = oleanolate + 3 [oxidized NADPH—hemoprotein reductase] + 4 H₂O (overall reaction)
(1a) β-amyrin + O₂ + [reduced NADPH—hemoprotein reductase] = erythrodiol + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) erythrodiol + O₂ + [reduced NADPH—hemoprotein reductase] = oleanolic aldehyde + [oxidized NADPH—hemoprotein reductase] + 2 H₂O
(1c) oleanolic aldehyde + O₂ + [reduced NADPH—hemoprotein reductase] = oleanolate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of β-amyrin, β-seco-amyrin, 11-oxo-β-amyrin and soysapogenol biosynthesis, click here

Other name(s):

CYP716A52v2; CYP716A12; CYP16A75; β-amyrin 28-oxidase

Systematic name:

β-amyrin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (28-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein found in plants. The enzyme is involved in the biosynthesis of oleanane-type triterpenoids, such as ginsenoside Ro. The enzyme from Medicago truncatula (barrel medic) (CYP716A12) can also convert α-amyrin and lupeol to ursolic acid and betulinic acid, respectively. The enzyme from Maesa lanceolata (false assegai) (CYP16A75) does not catalyse the reaction to completion, resulting in accumulation of both intermediates.

Links to other databases:

References:

1.	Fukushima, E.O., Seki, H., Ohyama, K., Ono, E., Umemoto, N., Mizutani, M., Saito, K. and Muranaka, T. CYP716A subfamily members are multifunctional oxidases in triterpenoid biosynthesis. Plant Cell Physiol. 52 (2011) 2050–2061. [DOI] [PMID: 22039103]
2.	Han, J.Y., Kim, M.J., Ban, Y.W., Hwang, H.S. and Choi, Y.E. The involvement of β-amyrin 28-oxidase (CYP716A52v2) in oleanane-type ginsenoside biosynthesis in Panax ginseng. Plant Cell Physiol. 54 (2013) 2034–2046. [DOI] [PMID: 24092881]
3.	Moses, T., Pollier, J., Faizal, A., Apers, S., Pieters, L., Thevelein, J.M., Geelen, D. and Goossens, A. Unraveling the triterpenoid saponin biosynthesis of the African shrub Maesa lanceolata. Mol. Plant 8 (2015) 122–135. [DOI] [PMID: 25578277]

[EC 1.14.14.126 created 2015 as EC 1.14.13.201, transferred 2018 to EC 1.14.14.126]

1.14.14.127

Accepted name:

methyl farnesoate epoxidase

Reaction:

methyl (2E,6E)-farnesoate + [reduced NADPH—hemoprotein reductase] + O₂ = juvenile hormone III + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of juvenile hormone biosynthesis, click here

Glossary:

juvenile hormone III = methyl (2E,6E,10R)-10,11-epoxy-3,7,11-trimethyldodeca-2,6-dienoate

Other name(s):

CYP15A1

Systematic name:

methyl (2E,6E)-farnesoate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase

Comments:

A cytochrome P-450 (heme-thiolate) protein. The enzyme, found in insects except for Lepidoptera (moths and butterflies) is specific for methyl farnesoate (cf. EC 1.14.14.128, farnesoate epoxidase) [1,2].

Links to other databases:

References:

1.	Helvig, C., Koener, J.F., Unnithan, G.C. and Feyereisen, R. CYP15A1, the cytochrome P450 that catalyzes epoxidation of methyl farnesoate to juvenile hormone III in cockroach corpora allata. Proc. Natl. Acad. Sci. USA 101 (2004) 4024–4029. [DOI] [PMID: 15024118]
2.	Daimon, T. and Shinoda, T. Function, diversity, and application of insect juvenile hormone epoxidases (CYP15). Biotechnol. Appl. Biochem. 60 (2013) 82–91. [DOI] [PMID: 23586995]

[EC 1.14.14.127 created 2015 as EC 1.14.13.202, transferred 2018 to EC 1.14.14.127]

1.14.14.128

Accepted name:

farnesoate epoxidase

Reaction:

(2E,6E)-farnesoate + [reduced NADPH—hemoprotein reductase] + O₂ = juvenile-hormone-III carboxylate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of juvenile hormone biosynthesis, click here

Glossary:

juvenile-hormone-III carboxylate = (2E,6E,10R)-10,11-epoxy-3,7,11-trimethyldodeca-2,6-dienoate

Other name(s):

CYP15C1

Systematic name:

(2E,6E)-farnesoate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase

Comments:

A cytochrome P-450 (heme-thiolate) protein. The enzyme, found in Lepidoptera (moths and butterflies), is specific for farnesoate (cf. EC 1.14.14.127, methyl farnesoate epoxidase) [1,2]. It is involved in the synthesis of juvenile hormone.

Links to other databases:

References:

1.	Daimon, T., Kozaki, T., Niwa, R., Kobayashi, I., Furuta, K., Namiki, T., Uchino, K., Banno, Y., Katsuma, S., Tamura, T., Mita, K., Sezutsu, H., Nakayama, M., Itoyama, K., Shimada, T. and Shinoda, T. Precocious metamorphosis in the juvenile hormone-deficient mutant of the silkworm, Bombyx mori. PLoS Genet. 8:e1002486 (2012). [DOI] [PMID: 22412378]
2.	Daimon, T. and Shinoda, T. Function, diversity, and application of insect juvenile hormone epoxidases (CYP15). Biotechnol. Appl. Biochem. 60 (2013) 82–91. [DOI] [PMID: 23586995]

[EC 1.14.14.128 created 2015 as EC 1.14.13.203, transferred 2018 to EC 1.14.14.128]

1.14.14.129

Accepted name:

long-chain acyl-CoA ω-monooxygenase

Reaction:

(1) oleoyl-CoA + [reduced NADPH—hemoprotein reductase] + O₂ = 18-hydroxyoleoyl-CoA + [oxidized NADPH—hemoprotein reductase] + H₂O
(2) linoleoyl-CoA + [reduced NADPH—hemoprotein reductase] + O₂ = 18-hydroxylinoleoyl-CoA + [oxidized NADPH—hemoprotein reductase] + H₂O

Other name(s):

long-chain acyl-CoA ω-hydroxylase; CYP86A₂2 (gene name)

Systematic name:

long-chain acyl-CoA,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (ω-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. The enzymes from solanaceous plants are involved in the biosynthesis of stigmatic estolide, a lipid-based polyester that forms a major component of the exudate.

Links to other databases:

References:

1.	Han, J., Clement, J.M., Li, J., King, A., Ng, S. and Jaworski, J.G. The cytochrome P450 CYP86A22 is a fatty acyl-CoA ω-hydroxylase essential for estolide synthesis in the stigma of Petunia hybrida. J. Biol. Chem. 285 (2010) 3986–3996. [DOI] [PMID: 19940120]

[EC 1.14.14.129 created 2015 as EC 1.14.13.204, transferred 2018 to EC 1.14.14.129]

1.14.14.130

Accepted name:

laurate 7-monooxygenase

Reaction:

dodecanoate + [reduced NADPH—hemoprotein reductase] + O₂ = 7-hydroxydodecanoate + [oxidized NADPH—hemoprotein reductase] + H₂O

Glossary:

laurate = dodecanoate

Other name(s):

CYP703A2 (gene name)

Systematic name:

dodecanoate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (7-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein found in plants. The enzyme is involved in the synthesis of sporopollenin - a complex polymer found at the outer layer of spores and pollen. It can also act on decanoate (C₁₀), myristate (C₁₄), and palmitate (C₁₆) with lower activity. The enzyme also produces a small amount of products that are hydroxylated at neighboring positions (C-6, C-8 and C-9).

Links to other databases:

References:

Morant, M., Jørgensen, K., Schaller, H., Pinot, F., Møller, B.L., Werck-Reichhart, D. and Bak, S. CYP703 is an ancient cytochrome P450 in land plants catalyzing in-chain hydroxylation of lauric acid to provide building blocks for sporopollenin synthesis in pollen. Plant Cell 19 (2007) 1473–1487. [DOI] [PMID: 17496121]

[EC 1.14.14.130 created 2015 as EC 1.14.13.206, transferred 2018 to EC 1.14.14.130]

1.14.14.131

Accepted name:

bursehernin 5′-monooxygenase

Reaction:

(–)-bursehernin + [reduced NADPH—hemoprotein reductase] + O₂ = (–)-5′-demethylyatein + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of podophyllotoxin biosynthesis, click here

Glossary:

(–)-bursehernin = (3R,4R)-4-(2H-1,3-benzodioxol-5-ylmethyl)-3-[(3,4-dimethoxyphenyl)methyl]oxolan-2-one
(–)-5′-demethylyatein = (3R,4R)-4-(2H-1,3-benzodioxol-5-ylmethyl)-3-[(3-hydroxy-4,5-dimethoxyphenyl)methyl]oxolan-2-one
(–)-yaetin = (3R,4R)-4-(2H-1,3-benzodioxol-5-ylmethyl)-3-[(3,4,5-trimethoxyphenyl)methyl]oxolan-2-one

Other name(s):

CYP71CU1 (gene name); bursehernin 5′-hydroxylase

Systematic name:

(–)-bursehernin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (5′-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein characterized from the plant Sinopodophyllum hexandrum. The enzyme is involved in the biosynthetic pathway of podophyllotoxin, a non-alkaloid toxin lignan whose derivatives are important anticancer drugs.

Links to other databases:

References:

1.	Lau, W. and Sattely, E.S. Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone. Science 349 (2015) 1224–1228. [DOI] [PMID: 26359402]

[EC 1.14.14.131 created 2016 as EC 1.14.13.213, transferred 2018 to EC 1.14.14.131]

1.14.14.132

Accepted name:

(–)-4′-demethyl-deoxypodophyllotoxin 4-hydroxylase

Reaction:

(–)-4′-demethyldeoxypodophyllotoxin + [reduced NADPH—hemoprotein reductase] + O₂ = (–)-4′-demethylepipodophyllotoxin + [oxidized NADPH—hemoprotein reductase] + H₂O

Glossary:

(–)-4′-demethyldeoxypodophyllotoxin = (5R,5aR,8aR)-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3′,4′:6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one
(–)-4′-demethylepipodophyllotoxin = (5R,5aR,8aR,9S)-9-hydroxy-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3′,4′:6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one

Other name(s):

CYP82D61 (gene name)

Systematic name:

(–)-deoxypodophyllotoxin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (4-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein characterized from the plant Sinopodophyllum hexandrum. The enzyme produces the direct precursor to etoposide, a potent anticancer drug. It can also act on (–)-deoxypodophyllotoxin with lower efficiency.

Links to other databases:

References:

1.	Lau, W. and Sattely, E.S. Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone. Science 349 (2015) 1224–1228. [DOI] [PMID: 26359402]

[EC 1.14.14.132 created 2016 as EC 1.14.13.214, transferred 2018 to EC 1.14.14.132]

1.14.14.133

Accepted name:

1,8-cineole 2-endo-monooxygenase

Reaction:

1,8-cineole + [reduced flavodoxin] + O₂ = 2-endo-hydroxy-1,8-cineole + [oxidized flavodoxin] + H₂O

For diagram of 1,8-cineole catabolism, click here

Glossary:

1,8-cineole = 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane
2-endo-hydroxy-1,8-cineole = (1R,4S,6R)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ol

Other name(s):

P450_cin; CYP176A; CYP176A1

Systematic name:

1,8-cineole,[reduced flavodoxin]:oxygen oxidoreductase (2-endo-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein that uses a flavodoxin-like redox partner to reduce the heme iron. Isolated from the bacterium Citrobacter braakii, which can use 1,8-cineole as the sole source of carbon.

Links to other databases:

References:

1.	Hawkes, D.B., Adams, G.W., Burlingame, A.L., Ortiz de Montellano, P.R. and De Voss, J.J. Cytochrome P450_cin (CYP176A), isolation, expression, and characterization. J. Biol. Chem. 277 (2002) 27725–27732. [DOI] [PMID: 12016226]
2.	Meharenna, Y.T., Li, H., Hawkes, D.B., Pearson, A.G., De Voss, J. and Poulos, T.L. Crystal structure of P450_cin in a complex with its substrate, 1,8-cineole, a close structural homologue to D-camphor, the substrate for P450_cam. Biochemistry 43 (2004) 9487–9494. [DOI] [PMID: 15260491]
3.	Kimmich, N., Das, A., Sevrioukova, I., Meharenna, Y., Sligar, S.G. and Poulos, T.L. Electron transfer between cytochrome P450_cin and its FMN-containing redox partner, cindoxin. J. Biol. Chem. 282 (2007) 27006–27011. [DOI] [PMID: 17606612]
4.	Meharenna, Y.T., Slessor, K.E., Cavaignac, S.M., Poulos, T.L. and De Voss, J.J. The critical role of substrate-protein hydrogen bonding in the control of regioselective hydroxylation in p450cin. J. Biol. Chem. 283 (2008) 10804–10812. [DOI] [PMID: 18270198]

[EC 1.14.14.133 created 2012 as EC 1.14.13.156, transferred 2018 to EC 1.14.14.133]

1.14.14.134

Accepted name:

β-amyrin 24-hydroxylase

Reaction:

(1) β-amyrin + [reduced NADPH—hemoprotein reductase] + O₂ = 24-hydroxy-β-amyrin + [oxidized NADPH—hemoprotein reductase] + H₂O
(2) sophoradiol + [reduced NADPH—hemoprotein reductase] + O₂ = 24-hydroxysophoradiol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of soyasapogenol biosynthesis, click here

Glossary:

24-hydroxy-β-amyrin = olean-12-ene-3β,24-diol
24-hydroxysophoradiol = soyasapogenol B

Other name(s):

sophoradiol 24-hydroxylase; CYP93E1

Systematic name:

β-amyrin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (24-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. Found in plants and participates in the biosynthesis of soybean saponins.

Links to other databases:

References:

1.	Shibuya, M., Hoshino, M., Katsube, Y., Hayashi, H., Kushiro, T. and Ebizuka, Y. Identification of β-amyrin and sophoradiol 24-hydroxylase by expressed sequence tag mining and functional expression assay. FEBS J. 273 (2006) 948–959. [DOI] [PMID: 16478469]

[EC 1.14.14.134 created 2011 as EC 1.14.99.43, transferred 2018 to EC 1.14.14.134]

1.14.14.135

Accepted name:

glyceollin synthase

Reaction:

(1) (6aS,11aS)-3,6a,9-trihydroxy-2-prenylpterocarpan + [reduced NADPH—hemoprotein reductase] + O₂ = glyceollin II + [oxidized NADPH—hemoprotein reductase] + 2 H₂O
(2) (6aS,11aS)-3,6a,9-trihydroxy-2-prenylpterocarpan + [reduced NADPH—hemoprotein reductase] + O₂ = glyceollin III + [oxidized NADPH—hemoprotein reductase] + 2 H₂O
(3) (6aS,11aS)-3,6a,9-trihydroxy-4-prenylpterocarpan + [reduced NADPH—hemoprotein reductase] + O₂ = glyceollin I + [oxidized NADPH—hemoprotein reductase] + 2 H₂O

For diagram of glyceollin biosynthesis (part 2), click here

Glossary:

prenyl = 3-methylbut-2-en-1-yl

Other name(s):

dimethylallyl-3,6a,9-trihydroxypterocarpan cyclase

Systematic name:

(6aS,11aS)-3,6a,9-trihydroxy-2-prenylpterocarpan,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (cyclizing)

Comments:

A cytochrome P-450 (heme-thiolate) protein purified from soybean.

Links to other databases:

References:

1.	Welle, R. and Grisebach, H. Induction of phytoalexin synthesis in soybean: enzymatic cyclization of prenylated pterocarpans to glyceollin isomers. Arch. Biochem. Biophys. 263 (1988) 191–198. [DOI] [PMID: 3369863]

[EC 1.14.14.135 created 2004 as EC 1.14.13.85, transferred 2018 to EC 1.14.14.135]

1.14.14.136

Accepted name:

deoxysarpagine hydroxylase

Reaction:

10-deoxysarpagine + [reduced NADPH—hemoprotein reductase] + O₂ = sarpagine + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of geissoschizine and sarpagine biosynthesis, click here

Other name(s):

DOSH

Systematic name:

10-deoxysarpagine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (10-hydroxylating)

Comments:

A cytohrome P-450 (heme-thiolate) protein isolated from the plant Rauvolfia serpentina.

Links to other databases:

References:

1.	Yu, B., Ruppert, M. and Stöckigt, J. Deoxysarpagine hydroxylase — a novel enzyme closing a short side pathway of alkaloid biosynthesis in Rauvolfia. Bioorg. Med. Chem. 10 (2002) 2479–2483. [DOI] [PMID: 12057637]

[EC 1.14.14.136 created 2005 as EC 1.14.13.91, transferred 2018 to EC 1.14.14.136]

1.14.14.137

Accepted name:

(+)-abscisic acid 8′-hydroxylase

Reaction:

(+)-abscisate + [reduced NADPH—hemoprotein reductase] + O₂ = 8′-hydroxyabscisate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of abscisic-acid biosynthesis, click here

Other name(s):

(+)-ABA 8′-hydroxylase; ABA 8′-hydroxylase; CYP707A1 (gene name)

Systematic name:

abscisate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (8′-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein found in plants. Catalyses the first step in the oxidative degradation of abscisic acid and is considered to be the pivotal enzyme in controlling the rate of degradation of this plant hormone [1]. CO inhibits the reaction, but its effects can be reversed by the presence of blue light [1]. The 8′-hydroxyabscisate formed can be converted into (–)-phaseic acid, most probably spontaneously.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 153190-37-5

References:

1.	Cutler, A.J., Squires, T.M., Loewen, M.K. and Balsevich, J.J. Induction of (+)-abscisic acid 8′ hydroxylase by (+)-abscisic acid in cultured maize cells. J. Exp. Bot. 48 (1997) 1787–1795.
2.	Krochko, J.E., Abrams, G.D., Loewen, M.K., Abrams, S.R. and Cutler, A.J. (+)-Abscisic acid 8′-hydroxylase is a cytochrome P₄₅₀ monooxygenase. Plant Physiol. 118 (1998) 849–860. [PMID: 9808729]
3.	Saito, S., Hirai, N., Matsumoto, C., Ohigashi, H., Ohta, D., Sakata, K. and Mizutani, M. Arabidopsis CYP707As encode (+)-abscisic acid 8′-hydroxylase, a key enzyme in the oxidative catabolism of abscisic acid. Plant Physiol. 134 (2004) 1439–1449. [PMID: 15064374]

[EC 1.14.14.137 created 2005 as EC 1.14.13.93, transferred 2018 EC 1.14.14.137]

1.14.14.138

Accepted name:

lithocholate 6β-hydroxylase

Reaction:

lithocholate + [reduced NADPH—hemoprotein reductase] + O₂ = 6β-hydroxylithocholate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of the reaction of deoxycholate and related bile acids, click here

Glossary:

lithocholate = 3α-hydroxy-5β-cholan-24-oate
6β-hydroxylithocholate = murideoxycholate = 3α,6β-dihydroxy-5β-cholan-24-oate

Other name(s):

lithocholate 6β-monooxygenase; CYP3A10; 6β-hydroxylase; cytochrome P450 3A10; lithocholic acid 6β-hydroxylase

Systematic name:

lithocholate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (6β-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein from Mesocricetus auratus (golden hamster). Expression of the gene for this enzyme is 50-fold higher in male compared to female hamsters [1].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 9075-83-6

References:

1.	Teixeira, J. and Gil, G. Cloning, expression, and regulation of lithocholic acid 6β-hydroxylase. J. Biol. Chem. 266 (1991) 21030–21036. [PMID: 1840595]
2.	Chang, T.K., Teixeira, J., Gil, G. and Waxman, D.J. The lithocholic acid 6beta-hydroxylase cytochrome P-450, CYP 3A10, is an active catalyst of steroid-hormone 6β-hydroxylation. Biochem. J. 291 (1993) 429–433. [PMID: 8484723]
3.	Subramanian, A., Wang, J. and Gil, G. STAT 5 and NF-Y are involved in expression and growth hormone-mediated sexually dimorphic regulation of cytochrome P₄₅₀ 3A10/lithocholic acid 6β-hydroxylase. Nucleic Acids Res. 26 (1998) 2173–2178. [DOI] [PMID: 9547277]
4.	Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137–174. [DOI] [PMID: 12543708]

[EC 1.14.14.138 created 2005 as EC 1.14.13.94, transferred 2018 to EC 1.14.14.138]

1.14.14.139

Accepted name:

5β-cholestane-3α,7α-diol 12α-hydroxylase

Reaction:

(1) 5β-cholestane-3α,7α-diol + [reduced NADPH—hemoprotein reductase] + O₂ = 5β-cholestane-3α,7α,12α-triol + [oxidized NADPH—hemoprotein reductase] + H₂O
(2) 7α-hydroxycholest-4-en-3-one + [reduced NADPH—hemoprotein reductase] + O₂ = 7α,12α-dihydroxycholest-4-en-3-one + [oxidized NADPH—hemoprotein reductase] + H₂O
(3) chenodeoxycholate + [reduced NADPH—hemoprotein reductase] + O₂ = cholate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of cholesterol catabolism (rings A, B and C), click here

Glossary:

chenodeoxycholate = 3α,7α-dihydroxy-5β-cholan-24-oate
cholate = 3α,7α-12α-trihydroxy-5β-cholan-24-oate

Other name(s):

5β-cholestane-3α,7α-diol 12α-monooxygenase; sterol 12α-hydroxylase (ambiguous); CYP8B1; cytochrome P450 8B1; 7α-hydroxycholest-4-en-3-one 12α-hydroxylase; 7α-hydroxy-4-cholesten-3-one 12α-monooxygenase; chenodeoxycholate 12α monooxygenase

Systematic name:

5β-cholestane-3α,7α-diol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (12α-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein found in mammals. This is the key enzyme in the biosynthesis of the bile acid cholate. The enzyme can also hydroxylate 5β-cholestane-3α,7α-diol at the 25 and 26 position, but to a lesser extent [2].

Links to other databases:

References:

1.	Hansson, R. and Wikvall, K. Hydroxylations in biosynthesis and metabolism of bile acids. Catalytic properties of different forms of cytochrome P-450. J. Biol. Chem. 255 (1980) 1643–1649. [PMID: 6766451]
2.	Hansson, R. and Wikvall, K. Hydroxylations in biosynthesis of bile acids. Cytochrome P-450 LM4 and 12α-hydroxylation of 5β-cholestane-3α,7α-diol. Eur. J. Biochem. 125 (1982) 423–429. [DOI] [PMID: 6811268]
3.	Ishida, H., Noshiro, M., Okuda, K. and Coon, M.J. Purification and characterization of 7α-hydroxy-4-cholesten-3-one 12α-hydroxylase. J. Biol. Chem. 267 (1992) 21319–21323. [PMID: 1400444]
4.	Eggertsen, G., Olin, M., Andersson, U., Ishida, H., Kubota, S., Hellman, U., Okuda, K.I. and Björkhem, I. Molecular cloning and expression of rabbit sterol 12α-hydroxylase. J. Biol. Chem. 271 (1996) 32269–32275. [DOI] [PMID: 8943286]
5.	Lundell, K. and Wikvall, K. Gene structure of pig sterol 12α-hydroxylase (CYP8B1) and expression in fetal liver: comparison with expression of taurochenodeoxycholic acid 6α-hydroxylase (CYP4A21). Biochim. Biophys. Acta 1634 (2003) 86–96. [DOI] [PMID: 14643796]
6.	del Castillo-Olivares, A. and Gil, G. α1-Fetoprotein transcription factor is required for the expression of sterol 12α -hydroxylase, the specific enzyme for cholic acid synthesis. Potential role in the bile acid-mediated regulation of gene transcription. J. Biol. Chem. 275 (2000) 17793–17799. [DOI] [PMID: 10747975]
7.	Yang, Y., Zhang, M., Eggertsen, G. and Chiang, J.Y. On the mechanism of bile acid inhibition of rat sterol 12α-hydroxylase gene (CYP8B1) transcription: roles of α-fetoprotein transcription factor and hepatocyte nuclear factor 4alpha. Biochim. Biophys. Acta 1583 (2002) 63–73. [DOI] [PMID: 12069850]
8.	Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137–174. [DOI] [PMID: 12543708]
9.	Fan, L., Joseph, J.F., Durairaj, P., Parr, M.K. and Bureik, M. Conversion of chenodeoxycholic acid to cholic acid by human CYP8B1. Biol. Chem. 400 (2019) 625–628. [DOI] [PMID: 30465713]

[EC 1.14.14.139 created 2005 as EC 1.14.13.96, transferred 2018 to EC 1.14.14.139 (EC 1.14.18.8 created 2005 as EC 1.14.13.95, transferred 2015 to EC 1.14.18.8, incorporated 2020) , modified 2020]

1.14.14.140

Transferred entry:

licodione synthase. Now included with EC 1.14.14.162, flavanone 2-hydroxylase

[EC 1.14.14.140 created 2004 as EC 1.14.13.87, transferred 2018 to EC 1.14.14.140, transferred 2018 to EC 1.14.14.162, deleted 2018]

1.14.14.141

Accepted name:

psoralen synthase

Reaction:

(+)-marmesin + [reduced NADPH—hemoprotein reductase] + O₂ = psoralen + [oxidized NADPH—hemoprotein reductase] + acetone + 2 H₂O

For diagram of reaction, click here

Glossary:

(+)-marmesin = (S)-2-(2-hydroxypropan-2-yl)-2,3-dihydro-7H-furo[3,2-g]chromen-7-one
psoralen = 7H-furo[3,2-g]chromen-7-one

Other name(s):

CYP71AJ1

Systematic name:

(+)-marmesin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase

Comments:

This microsomal cytochrome P-450 (heme-thiolate) enzyme is rather specific for (+)-marmesin, although it can also accept 5-hydroxymarmesin to a much lesser extent. Furanocoumarins protect plants from fungal invasion and herbivore attack. (+)-Columbianetin, the angular furanocoumarin analogue of the linear furanocoumarin (+)-marmesin, acts as a competitive inhibitor even though it is not a substrate.

Links to other databases:

References:

Larbat, R., Kellner, S., Specker, S., Hehn, A., Gontier, E., Hans, J., Bourgaud, F. and Matern, U. Molecular cloning and functional characterization of psoralen synthase, the first committed monooxygenase of furanocoumarin biosynthesis. J. Biol. Chem. 282 (2007) 542–554. [DOI] [PMID: 17068340]

[EC 1.14.14.141 created 2007 as EC 1.14.13.102, transferred 2018 to EC 1.14.14.141]

1.14.14.142

Accepted name:

8-dimethylallylnaringenin 2′-hydroxylase

Reaction:

sophoraflavanone B + [reduced NADPH—hemoprotein reductase] + O₂ = leachianone G + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of sophoraflavanone G biosynthesis, click here

Glossary:

dimethylallyl = prenyl = 3-methylbut-2-en-1-yl
lavandulyl = 5-methyl-2-(prop-1-en-2-yl)hex-4-en-1-yl
leachianone G = (–)-(2S)-2′-hydroxy-8-prenylnaringenin = (–)-(2S)-2-(2,4-dihydroxyphenyl)-5,7-dihydroxy-8-(3-methylbut-2-en-1-yl)-2,3-dihydro-4H-chromen-4-one
naringenin = 5,7-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one
sophoraflavanone B = (–)-(2S)-8-prenylnaringenin = (–)-(2S)-5,7-dihydroxy-2-(4-hydroxyphenyl)-8-(3-methylbut-2-en-1-yl)-2,3-dihydro-4H-chromen-4-one

Other name(s):

8-DMAN 2′-hydroxylase

Systematic name:

sophoraflavanone-B,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (2′-hydroxylating)

Comments:

A membrane-bound cytochrome P-450 (heme-thiolate) protein that is associated with the endoplasmic reticulum [1,2]. This enzyme is specific for sophoraflavanone B as substrate. Along with EC 2.5.1.70 (naringenin 8-dimethylallyltransferase) and EC 2.5.1.71 (leachianone G 2′′-dimethylallyltransferase), this enzyme forms part of the sophoraflavanone G biosynthetic pathway.

Links to other databases:

References:

1.	Yamamoto, H., Yatou, A. and Inoue, K. 8-Dimethylallylnaringenin 2′-hydroxylase, the crucial cytochrome P₄₅₀ mono-oxygenase for lavandulylated flavanone formation in Sophora flavescens cultured cells. Phytochemistry 58 (2001) 671–676. [DOI] [PMID: 11672730]
2.	Zhao, P., Inoue, K., Kouno, I. and Yamamoto, H. Characterization of leachianone G 2′′-dimethylallyltransferase, a novel prenyl side-chain elongation enzyme for the formation of the lavandulyl group of sophoraflavanone G in Sophora flavescens Ait. cell suspension cultures. Plant Physiol. 133 (2003) 1306–1313. [DOI] [PMID: 14551337]

[EC 1.14.14.142 created 2007 asEC 1.14.13.103, transferred 2018 to EC 1.14.14.142]

1.14.14.143

Accepted name:

(+)-menthofuran synthase

Reaction:

(+)-pulegone + [reduced NADPH—hemoprotein reductase] + O₂ = (+)-menthofuran + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of (â€“)-carvone, perillyl aldehyde and pulegone biosynthesis, click here and for mechanism of reaction, click here

Other name(s):

menthofuran synthase; (+)-pulegone 9-hydroxylase; (+)-MFS; cytochrome P450 menthofuran synthase

Systematic name:

(+)-pulegone,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (9-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. The conversion of substrate into product involves the hydroxylation of the syn-methyl (C₉), intramolecular cyclization to the hemiketal and dehydration to the furan [1]. This is the second cytochrome P-450-mediated step of monoterpene metabolism in peppermint, with the other step being catalysed by EC 1.14.14.99, (S)-limonene 3-monooxygenase [1].

Links to other databases:

References:

1.	Bertea, C.M., Schalk, M., Karp, F., Maffei, M. and Croteau, R. Demonstration that menthofuran synthase of mint (Mentha) is a cytochrome P₄₅₀ monooxygenase: cloning, functional expression, and characterization of the responsible gene. Arch. Biochem. Biophys. 390 (2001) 279–286. [DOI] [PMID: 11396930]
2.	Mahmoud, S.S. and Croteau, R.B. Menthofuran regulates essential oil biosynthesis in peppermint by controlling a downstream monoterpene reductase. Proc. Natl. Acad. Sci. USA 100 (2003) 14481–14486. [DOI] [PMID: 14623962]

[EC 1.14.14.143 created 2008 as EC 1.14.13.104, transferred 2018 to EC 1.14.14.143]

1.14.14.144

Accepted name:

abieta-7,13-diene hydroxylase

Reaction:

abieta-7,13-diene + [reduced NADPH—hemoprotein reductase] + O₂ = abieta-7,13-dien-18-ol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of abietadiene, abietate, isopimaradiene, labdadienol and sclareol biosynthesis, click here

Glossary:

abieta-7,13-diene = (4aS,4bR,10aS)-7-isopropyl-1,1,4a-trimethyl-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthrene
abieta-7,13-dien-18-ol = ((1R,4aR,4bR,10aR)-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthren-1-yl)methanol

Other name(s):

abietadiene hydroxylase (ambiguous)

Systematic name:

abieta-7,13-diene,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (18-hydroxylating)

Comments:

Links to other databases:

References:

1.	Funk, C. and Croteau, R. Diterpenoid resin acid biosynthesis in conifers: characterization of two cytochrome P450-dependent monooxygenases and an aldehyde dehydrogenase involved in abietic acid biosynthesis. Arch. Biochem. Biophys. 308 (1994) 258–266. [DOI] [PMID: 8311462]
2.	Funk, C., Lewinsohn, E., Vogel, B.S., Steele, C.L. and Croteau, R. Regulation of oleoresinosis in grand fir (Abies grandis) (coordinate induction of monoterpene and diterpene cyclases and two cytochrome P450-dependent diterpenoid hydroxylases by stem wounding). Plant Physiol. 106 (1994) 999–1005. [PMID: 12232380]

[EC 1.14.14.144 created 2009 as EC 1.14.13.108, modified 2012, transferred 2018 to EC 1.14.14.144]

1.14.14.145

Accepted name:

abieta-7,13-dien-18-ol hydroxylase

Reaction:

abieta-7,13-dien-18-ol + 2 [reduced NADPH—hemoprotein reductase] + 2 O₂ = abieta-7,13-dien-18-oate + 2 [oxidized NADPH—hemoprotein reductase] + 3 H₂O (overall reaction)
(1a) abieta-7,13-dien-18-ol + [reduced NADPH—hemoprotein reductase] + O₂ = abieta-7,13-dien-18,18-diol + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) abieta-7,13-dien-18,18-diol = abieta-7,13-dien-18-al + H₂O (spontaneous)
(1c) abieta-7,13-dien-18-al + [reduced NADPH—hemoprotein reductase] + O₂ = abieta-7,13-dien-18-oate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of abietadiene, abietate, isopimaradiene, labdadienol and sclareol biosynthesis, click here

Glossary:

abieta-7,13-dien-18-ol = ((1R,4aR,4bR,10aR)-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthren-1-yl)methanol
abieta-7,13-dien-18-al = (1R,4aR,4bR,10aR)-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthrene-1-carbaldehyde

Other name(s):

CYP720B1; PtAO; abietadienol hydroxylase (ambiguous)

Systematic name:

abieta-7,13-dien-18-ol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (18-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. This enzyme catalyses a step in the pathway of abietic acid biosynthesis. The activity has been demonstrated in cell-free stem extracts of Abies grandis (grand fir) and Pinus contorta (lodgepole pine) [1], and the gene encoding the enzyme has been identified in Pinus taeda (loblolly pine) [3]. The recombinant enzyme catalyses the oxidation of multiple diterpene alcohol and aldehydes, including levopimaradienol, isopimara-7,15-dienol, isopimara-7,15-dienal, dehydroabietadienol and dehydroabietadienal. It is not able to oxidize abietadiene.

Links to other databases:

References:

1.	Funk, C. and Croteau, R. Diterpenoid resin acid biosynthesis in conifers: characterization of two cytochrome P450-dependent monooxygenases and an aldehyde dehydrogenase involved in abietic acid biosynthesis. Arch. Biochem. Biophys. 308 (1994) 258–266. [DOI] [PMID: 8311462]
2.	Funk, C., Lewinsohn, E., Vogel, B.S., Steele, C.L. and Croteau, R. Regulation of oleoresinosis in grand fir (Abies grandis) (coordinate induction of monoterpene and diterpene cyclases and two cytochrome P450-dependent diterpenoid hydroxylases by stem wounding). Plant Physiol. 106 (1994) 999–1005. [PMID: 12232380]
3.	Ro, D.K., Arimura, G., Lau, S.Y., Piers, E. and Bohlmann, J. Loblolly pine abietadienol/abietadienal oxidase PtAO (CYP720B1) is a multifunctional, multisubstrate cytochrome P450 monooxygenase. Proc. Natl. Acad. Sci. USA 102 (2005) 8060–8065. [DOI] [PMID: 15911762]

[EC 1.14.14.145 created 2009 as EC 1.14.13.109, modified 2012, transferred 2018 to EC 1.14.14.145]

1.14.14.146

Accepted name:

geranylgeraniol 18-hydroxylase

Reaction:

geranylgeraniol + [reduced NADPH—hemoprotein reductase] + O₂ = 18-hydroxygeranylgeraniol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of acyclic diterpenoid biosynthesis, click here

Glossary:

plaunotol = 18-hydroxygeranylgeraniol

Other name(s):

GGOH-18-hydroxylase

Systematic name:

geranylgeraniol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (18-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein isolated from the plant Croton sublyratus.

Links to other databases:

References:

1.	Tansakul, P. and De-Eknamkul, W. Geranylgeraniol-18-hydroxylase: the last enzyme in the plaunotol biosynthetic pathway in Croton sublyratus. Phytochemistry 47 (1998) 1241–1246.

[EC 1.14.14.146 created 2009 as EC 1.14.13.110, transferred 2018 to EC 1.14.14.146]

1.14.14.147

Accepted name:

22α-hydroxysteroid 23-monooxygenase

Reaction:

(1) 3-epi-6-deoxocathasterone + [reduced NADPH—hemoprotein reductase] + O₂ = 6-deoxotyphasterol + [oxidized NADPH—hemoprotein reductase] + H₂O
(2) (22S,24R)-22-hydroxy-5α-ergostan-3-one + [reduced NADPH—hemoprotein reductase] + O₂ = 3-dehydro-6-deoxoteasterone + [oxidized NADPH—hemoprotein reductase] + H₂O

Other name(s):

cytochrome P450 90C1; CYP90D1; CYP90C1; 3-epi-6-deoxocathasterone,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (C-23-hydroxylating); 3-epi-6-deoxocathasterone 23-monooxygenase

Systematic name:

22α-hydroxysteroid,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (C-23-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein involved in brassinosteroid biosynthesis in plants. The enzyme has a relaxed substrate specificity, and C-23 hydroxylation can occur at different stages in the pathway. In Arabidopsis thaliana two isozymes, encoded by the CYP90C1 and CYP90D1 genes, have redundant activities.

Links to other databases:

References:

1.	Kim, G.T., Fujioka, S., Kozuka, T., Tax, F.E., Takatsuto, S., Yoshida, S. and Tsukaya, H. CYP90C1 and CYP90D1 are involved in different steps in the brassinosteroid biosynthesis pathway in Arabidopsis thaliana. Plant J. 41 (2005) 710–721. [DOI] [PMID: 15703058]
2.	Ohnishi, T., Szatmari, A.M., Watanabe, B., Fujita, S., Bancos, S., Koncz, C., Lafos, M., Shibata, K., Yokota, T., Sakata, K., Szekeres, M. and Mizutani, M. C-23 hydroxylation by Arabidopsis CYP90C1 and CYP90D1 reveals a novel shortcut in brassinosteroid biosynthesis. Plant Cell 18 (2006) 3275–3288. [DOI] [PMID: 17138693]

[EC 1.14.14.147 created 2010 as EC 1.14.13.112, transferred 2018 to EC 1.14.14.147, modified 2022]

1.14.14.148

Accepted name:

angelicin synthase

Reaction:

(+)-columbianetin + [reduced NADPH—hemoprotein reductase] + O₂ = angelicin + [oxidized NADPH—hemoprotein reductase] + acetone + 2 H₂O

For diagram of psoralen biosynthesis, click here

Other name(s):

CYP71AJ4 (gene name)

Systematic name:

(+)-columbianetin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase

Comments:

This cytochrome P-450 (heme-thiolate) enzyme from wild parsnip is involved in the formation of angular furanocoumarins. Attacks its substrate by syn-elimination of hydrogen from C-3′.

Links to other databases:

References:

Larbat, R., Hehn, A., Hans, J., Schneider, S., Jugde, H., Schneider, B., Matern, U. and Bourgaud, F. Isolation and functional characterization of CYP71AJ4 encoding for the first P₄₅₀ monooxygenase of angular furanocoumarin biosynthesis. J. Biol. Chem. 284 (2009) 4776–4785. [DOI] [PMID: 19098286]

[EC 1.14.14.148 created 2010 as EC 1.14.13.115, transferred 2018 to EC 1.14.14.148]

1.14.14.149

Accepted name:

5-epiaristolochene 1,3-dihydroxylase

Reaction:

5-epiaristolochene + 2 [reduced NADPH—hemoprotein reductase] + 2 O₂ = capsidiol + 2 [oxidized NADPH—hemoprotein reductase] + 2 H₂O

click here

Other name(s):

5-epi-aristolochene 1,3-dihydroxylase; EAH; CYP71D20

Systematic name:

5-epiaristolochene,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (1- and 3-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. Kinetic studies suggest that 1β-hydroxyepiaristolochene is mainly formed first followed by hydroxylation at C-3. However the reverse order via 3α-hydroxyepiaristolochene does occur.

Links to other databases:

References:

1.	Ralston, L., Kwon, S.T., Schoenbeck, M., Ralston, J., Schenk, D.J., Coates, R.M. and Chappell, J. Cloning, heterologous expression, and functional characterization of 5-epi-aristolochene-1,3-dihydroxylase from tobacco (Nicotiana tabacum). Arch. Biochem. Biophys. 393 (2001) 222–235. [DOI] [PMID: 11556809]
2.	Takahashi, S., Zhao, Y., O'Maille, P.E., Greenhagen, B.T., Noel, J.P., Coates, R.M. and Chappell, J. Kinetic and molecular analysis of 5-epiaristolochene 1,3-dihydroxylase, a cytochrome P₄₅₀ enzyme catalyzing successive hydroxylations of sesquiterpenes. J. Biol. Chem. 280 (2005) 3686–3696. [DOI] [PMID: 15522862]

[EC 1.14.14.149 created 2011 as EC 1.14.13.119, transferred 2018 to EC 1.14.14.149]

1.14.14.150

Accepted name:

costunolide synthase

Reaction:

germacra-1(10),4,11(13)-trien-12-oate + [reduced NADPH—hemoprotein reductase] + O₂ = (+)-costunolide + [oxidized NADPH—hemoprotein reductase] + 2 H₂O (overall reaction)
(1a) germacra-1(10),4,11(13)-trien-12-oate + [reduced NADPH—hemoprotein reductase] + O₂ = 6α-hydroxygermacra-1(10),4,11(13)-trien-12-oate + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) 6α-hydroxygermacra-1(10),4,11(13)-trien-12-oate = (+)-costunolide + H₂O (spontaneous)

click here

Other name(s):

CYP71BL2

Systematic name:

germacra-1(10),4,11(13)-trien-12-oate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (6α-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein from chicory plants. The enzyme hydroxylates carbon C-6 of germacra-1(10),4,11(13)-trien-12-oate to give 6α-hydroxygermacra-1(10),4,11(13)-trien-12-oate, which spontaneously cyclises to form the lactone ring.

Links to other databases:

References:

de Kraker, J.W., Franssen, M.C., Joerink, M., de Groot, A. and Bouwmeester, H.J. Biosynthesis of costunolide, dihydrocostunolide, and leucodin. Demonstration of cytochrome p₄₅₀-catalyzed formation of the lactone ring present in sesquiterpene lactones of chicory. Plant Physiol. 129 (2002) 257–268. [DOI] [PMID: 12011356]

[EC 1.14.14.150 created 2011 as EC 1.14.13.120, transferred 2018 to EC 1.14.14.150]

1.14.14.151

Accepted name:

premnaspirodiene oxygenase

Reaction:

(–)-vetispiradiene + 2 [reduced NADPH—hemoprotein reductase] + 2 O₂ = solavetivone + 2 [oxidized NADPH—hemoprotein reductase] + 3 H₂O (overall reaction)
(1a) (–)-vetispiradiene + [reduced NADPH—hemoprotein reductase] + O₂ = solavetivol + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) solavetivol + [reduced NADPH—hemoprotein reductase] + O₂ = solavetivone + [oxidized NADPH—hemoprotein reductase] + 2 H₂O

For diagram of solavetivone biosynthesis, click here

Glossary:

(–)-premnaspirodiene = (–)-vetispiradiene

Other name(s):

HPO; Hyoscymus muticus premnaspirodiene oxygenase; CYP71D55

Systematic name:

(–)-vetispiradiene,[reduced NADPH—hemoprotein reductase]:oxygen 2α-oxidoreductase

Comments:

A cytochrome P-450 (heme-thiolate) protein. The enzyme from the plant Hyoscymus muticus also hydroxylates valencene at C-2 to give the α-hydroxy compound, nootkatol, and this is converted into nootkatone. 5-Epiaristolochene and epieremophilene are hydroxylated at C-2 to give a 2β-hydroxy derivatives that are not oxidized further.

Links to other databases:

References:

Takahashi, S., Yeo, Y.S., Zhao, Y., O'Maille, P.E., Greenhagen, B.T., Noel, J.P., Coates, R.M. and Chappell, J. Functional characterization of premnaspirodiene oxygenase, a cytochrome P₄₅₀ catalyzing regio- and stereo-specific hydroxylations of diverse sesquiterpene substrates. J. Biol. Chem. 282 (2007) 31744–31754. [DOI] [PMID: 17715131]

[EC 1.14.14.151 created 2011 as EC 1.14.13.121, transferred 2018 to EC 1.14.14.151]

1.14.14.152

Accepted name:

β-amyrin 11-oxidase

Reaction:

β-amyrin + 2 [reduced NADPH—hemoprotein reductase] + 2 O₂ = 11-oxo-β-amyrin + 2 [oxidized NADPH—hemoprotein reductase] + 3 H₂O (overall reaction)
(1a) β-amyrin + [reduced NADPH—hemoprotein reductase] + O₂ = 11α-hydroxy-β-amyrin + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) 11α-hydroxy-β-amyrin + [reduced NADPH—hemoprotein reductase] + O₂ = 11-oxo-β-amyrin + [oxidized NADPH—hemoprotein reductase] + 2 H₂O

For diagram of glycyrrhenate biosynthesis, click here

Other name(s):

CYP88D6

Systematic name:

β-amyrin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein from the plant Glycyrrhiza uralensis (Chinese licorice) that participates in the glycyrrhizin biosynthesis pathway. The enzyme is also able to oxidize 30-hydroxy-β-amyrin to 11α,30-dihydroxy-β-amyrin but this is not thought to be part of glycyrrhizin biosynthesis.

Links to other databases:

References:

Seki, H., Ohyama, K., Sawai, S., Mizutani, M., Ohnishi, T., Sudo, H., Akashi, T., Aoki, T., Saito, K. and Muranaka, T. Licorice β-amyrin 11-oxidase, a cytochrome P₄₅₀ with a key role in the biosynthesis of the triterpene sweetener glycyrrhizin. Proc. Natl. Acad. Sci. USA 105 (2008) 14204–14209. [DOI] [PMID: 18779566]

[EC 1.14.14.152 created 2011 as EC 1.14.13.134, transferred 2018 to EC 1.14.14.152]

1.14.14.153

Accepted name:

indole-2-monooxygenase

Reaction:

indole + [reduced NADPH—hemoprotein reductase] + O₂ = indolin-2-one + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of benzoxazinone biosynthesis, click here

Other name(s):

BX2 (gene name); CYP71C4 (gene name)

Systematic name:

indole,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (2-hydroxylating)

Comments:

Links to other databases:

References:

1.	Frey, M., Chomet, P., Glawischnig, E., Stettner, C., Grün, S., Winklmair, A., Eisenreich, W., Bacher, A., Meeley, R.B., Briggs, S.P., Simcox, K. and Gierl, A. Analysis of a chemical plant defense mechanism in grasses. Science 277 (1997) 696–699. [DOI] [PMID: 9235894]
2.	Glawischnig, E., Grun, S., Frey, M. and Gierl, A. Cytochrome P450 monooxygenases of DIBOA biosynthesis: specificity and conservation among grasses. Phytochemistry 50 (1999) 925–930. [DOI] [PMID: 10385992]

[EC 1.14.14.153 created 2012 as EC 1.14.13.137, transferred 2018 to EC 1.14.14.153]

1.14.14.154

Accepted name:

sterol 14α-demethylase

Reaction:

a 14α-methylsteroid + 3 [reduced NADPH—hemoprotein reductase] + 3 O₂ = a Δ¹⁴-steroid + formate + 3 [oxidized NADPH—hemoprotein reductase] + 4 H₂O (overall reaction)
(1a) a 14α-methylsteroid + [reduced NADPH—hemoprotein reductase] + O₂ = a 14α-hydroxymethylsteroid + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) a 14α-hydroxysteroid + [reduced NADPH—hemoprotein reductase] + O₂ = a 14α-formylsteroid + [oxidized NADPH—hemoprotein reductase] + 2 H₂O
(1c) a 14α-formylsteroid + [reduced NADPH—hemoprotein reductase] + O₂ = a Δ¹⁴-steroid + formate + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of sterol ring B, C, D modification, click here

Glossary:

obtusifoliol = 4α,14α-dimethyl-5α-ergosta-8,24(28)-dien-3β-ol or 4α,14α-dimethyl-24-methylene-5α-cholesta-8-en-3β-ol

Other name(s):

obtusufoliol 14-demethylase; lanosterol 14-demethylase; lanosterol 14α-demethylase; sterol 14-demethylase; CYP51 (gene name); ERG11 (gene name)

Systematic name:

sterol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (14-methyl cleaving)

Comments:

This cytochrome P-450 (heme-thiolate) enzyme acts on a range of steroids with a 14α-methyl group, such as obtusifoliol and lanosterol. The enzyme catalyses a hydroxylation and a reduction of the 14α-methyl group, followed by a second hydroxylation, resulting in the elimination of formate and formation of a 14(15) double bond.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 60063-87-8

References:

1.	Alexander, K., Akhtar, M., Boar, R.B., McGhie, J.F. and Barton, D.H.R. The removal of the 32-carbon atom as formic acid in cholesterol biosynthesis. J. Chem. Soc. Chem. Commun. (1972) 383–385.
2.	Yoshida, Y. and Aoyama, Y. Yeast cytochrome P-450 catalyzing lanosterol 14 α-demethylation. I. Purification and spectral properties. J. Biol. Chem. 259 (1984) 1655–1660. [PMID: 6363414]
3.	Aoyama, Y., Yoshida, Y. and Sato, R. Yeast cytochrome P-450 catalyzing lanosterol 14 α-demethylation. II. Lanosterol metabolism by purified P-450¹⁴DM and by intact microsomes. J. Biol. Chem. 259 (1984) 1661–1666. [PMID: 6420412]
4.	Aoyama, Y. and Yoshida, Y. Different substrate specificities of lanosterol 14α-demethylase (P-450_14DM) of Saccharomyces cerevisiae and rat liver of 24-methylene-24,25-dihydrolanosterol and 24,25-dihydrolanosterol. Biochem. Biophys. Res. Commun. 178 (1991) 1064–1071. [DOI] [PMID: 1872829]
5.	Aoyama, Y. and Yoshida, Y. The 4β-methyl group of substrate does not affect the activity of lanosterol 14α-demethylase (P₄₅₀14DM) of yeast: differences between the substrate recognition by yeast and plant sterol 14α-demethylases. Biochem. Biophys. Res. Commun. 183 (1992) 1266–1272. [DOI] [PMID: 1567403]
6.	Bak, S., Kahn, R.A., Olsen, C.E. and Halkier, B.A. Cloning and expression in Escherichia coli of the obtusifoliol 14α-demethylase of Sorghum bicolor (L.) Moench, a cytochrome P₄₅₀ orthologous to the sterol 14α-demethylases (CYP51) from fungi and mammals. Plant J. 11 (1997) 191–201. [DOI] [PMID: 9076987]

[EC 1.14.14.154 created 2001 as EC 1.14.13.70, modified 2013, transferred 2018 EC 1.14.14.154]

1.14.14.155

Accepted name:

3,6-diketocamphane 1,2-monooxygenase

Reaction:

(–)-bornane-2,5-dione + O₂ + FMNH₂ = (–)-5-oxo-1,2-campholide + FMN + H₂O

Glossary:

(–)-bornane-2,5-dione = 3,6-diketocamphane

Other name(s):

3,6-diketocamphane lactonizing enzyme; 3,6-DKCMO

Systematic name:

(–)-bornane-2,5-dione,FMNH₂:oxygen oxidoreductase (1,2-lactonizing)

Comments:

A Baeyer-Villiger monooxygenase isolated from camphor-grown strains of Pseudomonas putida and encoded on the cam plasmid. Involved in the degradation of (–)-camphor. Requires a dedicated NADH—FMN reductase [cf. EC 1.5.1.42, FMN reductase (NADH)] [1,2]. The product spontaneously converts to [(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetate.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, KEGG, PDB

References:

Iwaki, H., Grosse, S., Bergeron, H., Leisch, H., Morley, K., Hasegawa, Y. and Lau, P.C. Camphor pathway redux: functional recombinant expression of 2,5- and 3,6-diketocamphane monooxygenases of Pseudomonas putida ATCC 17453 with their cognate flavin reductase catalyzing Baeyer-Villiger reactions. Appl. Environ. Microbiol. 79 (2013) 3282–3293. [PMID: 23524667]

Isupov, M.N., Schroder, E., Gibson, R.P., Beecher, J., Donadio, G., Saneei, V., Dcunha, S.A., McGhie, E.J., Sayer, C., Davenport, C.F., Lau, P.C., Hasegawa, Y., Iwaki, H., Kadow, M., Balke, K., Bornscheuer, U.T., Bourenkov, G. and Littlechild, J.A. The oxygenating constituent of 3,6-diketocamphane monooxygenase from the CAM plasmid of Pseudomonas putida: the first crystal structure of a type II Baeyer-Villiger monooxygenase. Acta Crystallogr. D Biol. Crystallogr. 71 (2015) 2344–2353. [PMID: 26527149]

[EC 1.14.14.155 created 2018]

1.14.14.156

Accepted name:

tryptophan N-monooxygenase

Reaction:

L-tryptophan + 2 [reduced NADPH—hemoprotein reductase] + 2 O₂ = (E)-indol-3-ylacetaldoxime + 2 [oxidized NADPH—hemoprotein reductase] + CO₂ + 3 H₂O (overall reaction)
(1a) L-tryptophan + [reduced NADPH—hemoprotein reductase] + O₂ = N-hydroxy-L-tryptophan + [oxidized NADPH—hemoprotein reductase] + H₂O
(1b) N-hydroxy-L-tryptophan + [reduced NADPH—hemoprotein reductase] + O₂ = N,N-dihydroxy-L-tryptophan + [oxidized NADPH—hemoprotein reductase] + H₂O
(1c) N,N-dihydroxy-L-tryptophan = (E)-indol-3-ylacetaldoxime + CO₂ + H₂O

Other name(s):

tryptophan N-hydroxylase; CYP79B1; CYP79B2; CYP79B3

Systematic name:

L-tryptophan,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (N-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein from the plant Arabidopsis thaliana. This enzyme catalyses two successive N-hydroxylations of L-tryptophan, the first steps in the biosynthesis of both auxin and the indole alkaloid phytoalexin camalexin. The product of the two hydroxylations, N,N-dihydroxy-L-tryptophan, is extremely labile and dehydrates spontaneously. The dehydrated product is then subject to a decarboxylation that produces an oxime. It is still not known whether the decarboxylation is spontaneous or catalysed by the enzyme.

Links to other databases:

References:

1.	Mikkelsen, M.D., Hansen, C.H., Wittstock, U. and Halkier, B.A. Cytochrome P₄₅₀ CYP79B2 from Arabidopsis catalyzes the conversion of tryptophan to indole-3-acetaldoxime, a precursor of indole glucosinolates and indole-3-acetic acid. J. Biol. Chem. 275 (2000) 33712–33717. [DOI] [PMID: 10922360]
2.	Hull, A.K., Vij, R. and Celenza, J.L. Arabidopsis cytochrome P₄₅₀s that catalyze the first step of tryptophan-dependent indole-3-acetic acid biosynthesis. Proc. Natl. Acad. Sci. USA 97 (2000) 2379–2384. [DOI] [PMID: 10681464]
3.	Zhao, Y., Hull, A.K., Gupta, N.R., Goss, K.A., Alonso, J., Ecker, J.R., Normanly, J., Chory, J. and Celenza, J.L. Trp-dependent auxin biosynthesis in Arabidopsis: involvement of cytochrome P₄₅₀s CYP79B2 and CYP79B3. Genes Dev. 16 (2002) 3100–3112. [DOI] [PMID: 12464638]
4.	Naur, P., Hansen, C.H., Bak, S., Hansen, B.G., Jensen, N.B., Nielsen, H.L. and Halkier, B.A. CYP79B1 from Sinapis alba converts tryptophan to indole-3-acetaldoxime. Arch. Biochem. Biophys. 409 (2003) 235–241. [DOI] [PMID: 12464264]

[EC 1.14.14.156 created 2011 as EC 1.14.13.125, transferred 2018 to EC 1.14.14.156]

1.14.14.157

Accepted name:

indolin-2-one monooxygenase

Reaction:

indolin-2-one + [reduced NADPH—hemoprotein reductase] + O₂ = 3-hydroxyindolin-2-one + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of benzoxazinone biosynthesis, click here

Other name(s):

BX3 (gene name); CYP71C2 (gene name)

Systematic name:

indolin-2-one,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (3-hydroxylating)

Comments:

Links to other databases:

References:

1.	Frey, M., Chomet, P., Glawischnig, E., Stettner, C., Grün, S., Winklmair, A., Eisenreich, W., Bacher, A., Meeley, R.B., Briggs, S.P., Simcox, K. and Gierl, A. Analysis of a chemical plant defense mechanism in grasses. Science 277 (1997) 696–699. [DOI] [PMID: 9235894]
2.	Glawischnig, E., Grun, S., Frey, M. and Gierl, A. Cytochrome P450 monooxygenases of DIBOA biosynthesis: specificity and conservation among grasses. Phytochemistry 50 (1999) 925–930. [DOI] [PMID: 10385992]

[EC 1.14.14.157 created 2012 as EC 1.14.13.138, transferred 2018 to EC 1.14.14.157]

1.14.14.158

Accepted name:

carotenoid ε hydroxylase

Reaction:

(1) α-carotene + [reduced NADPH-hemoprotein reductase] + O₂ = α-cryptoxanthin + [oxidized NADPH-hemoprotein reductase] + H₂O
(2) zeinoxanthin + [reduced NADPH-hemoprotein reductase] + O₂ = lutein + [oxidized NADPH-hemoprotein reductase] + H₂O

For diagram of lutein biosynthesis, click here

Other name(s):

CYP97C1; LUT1; CYP97C; carotene ε-monooxygenase

Systematic name:

α-carotene,[reduced NADPH-hemoprotein reductase]:oxygen oxidoreductase (3-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein.

Links to other databases:

References:

1.	Pogson, B., McDonald, K.A., Truong, M., Britton, G. and DellaPenna, D. Arabidopsis carotenoid mutants demonstrate that lutein is not essential for photosynthesis in higher plants. Plant Cell 8 (1996) 1627–1639. [DOI] [PMID: 8837513]
2.	Tian, L., Musetti, V., Kim, J., Magallanes-Lundback, M. and DellaPenna, D. The Arabidopsis LUT1 locus encodes a member of the cytochrome P₄₅₀ family that is required for carotenoid ε-ring hydroxylation activity. Proc. Natl. Acad. Sci. USA 101 (2004) 402–407. [DOI] [PMID: 14709673]
3.	Stigliani, A.L., Giorio, G. and D'Ambrosio, C. Characterization of P450 carotenoid β- and ε-hydroxylases of tomato and transcriptional regulation of xanthophyll biosynthesis in root, leaf, petal and fruit. Plant Cell Physiol. 52 (2011) 851–865. [PMID: 21450689]
4.	Chang, S., Berman, J., Sheng, Y., Wang, Y., Capell, T., Shi, L., Ni, X., Sandmann, G., Christou, P. and Zhu, C. Cloning and functional characterization of the maize (Zea mays L.) carotenoid ε hydroxylase gene. PLoS One 10:e0128758 (2015). [PMID: 26030746]
5.	Reddy, C.S., Lee, S.H., Yoon, J.S., Kim, J.K., Lee, S.W., Hur, M., Koo, S.C., Meilan, J., Lee, W.M., Jang, J.K., Hur, Y., Park, S.U. and Kim, A.YB. Molecular cloning and characterization of carotenoid pathway genes and carotenoid content in Ixeris dentata var. albiflora. Molecules 22 (2017) . [DOI] [PMID: 28858245]

[EC 1.14.14.158 created 2011 as EC 1.14.99.45, transferred 2018 to EC 1.14.14.158]

1.14.15.31

Accepted name:

2-hydroxy-5-methyl-1-naphthoate 7-hydroxylase

Reaction:

2-hydroxy-5-methyl-1-naphthoate + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = 2,7-dihydroxy-5-methyl-1-naphthoate + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O

For diagram of neocarzinostatin biosynthesis, click here

Other name(s):

NcsB3

Systematic name:

2-hydroxy-5-methyl-1-naphthoate,reduced ferredoxin:oxygen oxidoreductase (7-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein involved in the synthesis of neocarzinostatin in the bacterium Streptomyces carzinostaticus.

Links to other databases:

References:

1.	Hang, V.T.T., Oh, T.J., Yamaguchi, T. and Sohng, J.K. In vivo characterization of NcsB3 to establish the complete biosynthesis of the naphthoic acid moiety of the neocarzinostatin chromophore. FEMS Microbiol. Lett. 311 (2010) 119–125. [DOI] [PMID: 20735485]

[EC 1.14.15.31 created 2014 as EC 1.14.99.49, transferred 2018 to EC 1.14.15.31]

1.14.15.32

Accepted name:

pentalenene oxygenase

Reaction:

pentalenene + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H⁺ + 2 O₂ = pentalen-13-al + 4 oxidized ferredoxin [iron-sulfur] cluster + 3 H₂O (overall reaction)
(1a) pentalenene + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = pentalen-13-ol + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O
(1b) pentalen-13-ol + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = pentalen-13-al + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H₂O

For diagram of humulene-based sequiterpenoid biosynthesis, click here

Other name(s):

PtlI

Systematic name:

pentalenene,reduced ferredoxin:oxygen 13-oxidoreductase

Comments:

A cytochrome P-450 (heme-thiolate) protein found in the bacterium Streptomyces avermitilis. The enzyme is involved in the biosynthesis of pentalenolactone and related antibiotics.

Links to other databases:

References:

1.	Quaderer, R., Omura, S., Ikeda, H. and Cane, D.E. Pentalenolactone biosynthesis. Molecular cloning and assignment of biochemical function to PtlI, a cytochrome P₄₅₀ of Streptomyces avermitilis. J. Am. Chem. Soc. 128 (2006) 13036–13037. [DOI] [PMID: 17017767]

[EC 1.14.15.32 created 2011 as EC 1.14.13.133, transferred 2018 to EC 1.14.15.32]

1.14.15.33

Accepted name:

pikromycin synthase

Reaction:

(1) narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = pikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O
(2) narbomycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = neopikromycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O
(3) narbomycin + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H⁺ + 2 O₂ = novapikromycin + 4 oxidized ferredoxin [iron-sulfur] cluster + 2 H₂O
(4) 10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = methymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O
(5) 10-deoxymethymycin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = neomethymycin + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O
(6) 10-deoxymethymycin + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H⁺ + 2 O₂ = novamethymycin + 4 oxidized ferredoxin [iron-sulfur] cluster + 2 H₂O

For diagram of methymycin biosynthesis, click here and for diagram of pikromycin biosynthesis, click here

Other name(s):

PikC; CYP107L1

Systematic name:

narbomycin,reduced ferredoxin:oxygen oxidoreductase (pikromycin-forming)

Comments:

A cytochrome P-450 (heme-thiolate) protein. Involved in the biosynthesis of a number of bacterial macrolide antibiotics containing a desosamine glycoside unit. With narbomycin it hydroxylates at either C-12 to give pikromycin or C-14 to give neopikromycin or both positions to give narvopikromycin. With 10-deoxymethymycin it hydroxylates at either C-10 to give methymycin or C-12 to give neomethymycin or both positions to give novamethymycin.

Links to other databases:

References:

1.	Xue, Y., Wilson, D., Zhao, L., Liu Hw and Sherman, D.H. Hydroxylation of macrolactones YC-17 and narbomycin is mediated by the pikC-encoded cytochrome P450 in Streptomyces venezuelae. Chem. Biol. 5 (1998) 661–667. [DOI] [PMID: 9831532]
2.	Sherman, D.H., Li, S., Yermalitskaya, L.V., Kim, Y., Smith, J.A., Waterman, M.R. and Podust, L.M. The structural basis for substrate anchoring, active site selectivity, and product formation by P450 PikC from Streptomyces venezuelae. J. Biol. Chem. 281 (2006) 26289–26297. [DOI] [PMID: 16825192]
3.	Li, S., Ouellet, H., Sherman, D.H. and Podust, L.M. Analysis of transient and catalytic desosamine-binding pockets in cytochrome P-450 PikC from Streptomyces venezuelae. J. Biol. Chem. 284 (2009) 5723–5730. [DOI] [PMID: 19124459]

[EC 1.14.15.33 created 2014 as EC 1.14.13.185, transferred 2018 to EC 1.14.15.33]

1.14.15.34

Accepted name:

20-oxo-5-O-mycaminosyltylactone 23-monooxygenase

Reaction:

20-oxo-5-O-β-mycaminosyltylactone + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = 5-O-β-mycaminosyltylonolide + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O

For diagram of tylosin biosynthesis, click here

Glossary:

tylactone = (4R,5S,6S,7S,9R,11E,13E,15S,16R)-7,16-diethyl-4,6-dihydroxy-5,9,13,15-tetramethyl-1-oxacyclohexadeca-11,13-diene-2,10-dione
α-D-mycaminose = 3-dimethylamino-3,6-dideoxy-α-D-glucopyranose
tylonolide = 2-[(4R,5S,6S,7R,9R,11E,13E,15R,16R)-16-ethyl-4,6-dihydroxy-15-(hydroxymethyl)-5,9,13-trimethyl-2,10-dioxo-1-oxacyclohexadeca-11,13-dien-7-yl]acetaldehyde

Other name(s):

tylH1 (gene name)

Systematic name:

20-oxo-5-O-β-mycaminosyltylactone,reduced ferredoxin:oxygen oxidoreductase (23-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein. Involved in the biosynthetic pathway of the macrolide antibiotic tylosin, which is produced by several species of Streptomyces bacteria.

Links to other databases:

References:

1.	Baltz, R.H. and Seno, E.T. Properties of Streptomyces fradiae mutants blocked in biosynthesis of the macrolide antibiotic tylosin. Antimicrob. Agents Chemother. 20 (1981) 214–225. [PMID: 7283418]
2.	Reeves, C.D., Ward, S.L., Revill, W.P., Suzuki, H., Marcus, M., Petrakovsky, O.V., Marquez, S., Fu, H., Dong, S.D. and Katz, L. Production of hybrid 16-membered macrolides by expressing combinations of polyketide synthase genes in engineered Streptomyces fradiae hosts. Chem. Biol. 11 (2004) 1465–1472. [DOI] [PMID: 15489173]

[EC 1.14.15.34 created 2014 as EC 1.14.13.186, transferred 2018 to EC 1.14.15.34]

1.14.15.35

Accepted name:

6-deoxyerythronolide B hydroxylase

Reaction:

6-deoxyerythronolide B + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = erythronolide B + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O

For diagram of erythromycin biosynthesis, click here

Other name(s):

DEB hydroxylase; eryF (gene name); P450(eryF); CYP107A1

Systematic name:

6-deoxyerythronolide-B,reduced ferredoxin:oxygen oxidoreductase

Comments:

A cytochrome P-450 (heme-thiolate) protein isolated from the bacterium Saccharopolyspora erythraea. The enzyme is involved in the biosynthesis of the antibiotic erythromycin.

Links to other databases:

References:

1.	Weber, J.M., Leung, J.O., Swanson, S.J., Idler, K.B. and McAlpine, J.B. An erythromycin derivative produced by targeted gene disruption in Saccharopolyspora erythraea. Science 252 (1991) 114–117. [DOI] [PMID: 2011746]
2.	Shafiee, A. and Hutchinson, C.R. Macrolide antibiotic biosynthesis: isolation and properties of two forms of 6-deoxyerythronolide B hydroxylase from Saccharopolyspora erythraea (Streptomyces erythreus). Biochemistry 26 (1987) 6204–6210. [PMID: 2446657]
3.	Cupp-Vickery, J.R., Li, H. and Poulos, T.L. Preliminary crystallographic analysis of an enzyme involved in erythromycin biosynthesis: cytochrome P450eryF. Proteins 20 (1994) 197–201. [DOI] [PMID: 7846029]
4.	Nagano, S., Cupp-Vickery, J.R. and Poulos, T.L. Crystal structures of the ferrous dioxygen complex of wild-type cytochrome P450eryF and its mutants, A245S and A245T: investigation of the proton transfer system in P450eryF. J. Biol. Chem. 280 (2005) 22102–22107. [DOI] [PMID: 15824115]

[EC 1.14.15.35 created 2014 as EC 1.14.13.188, transferred 2018 to EC 1.14.15.35]

1.14.19.62

Accepted name:

secologanin synthase

Reaction:

loganin + [reduced NADPH—hemoprotein reductase] + O₂ = secologanin + [oxidized NADPH—hemoprotein reductase] + 2 H₂O

For diagram of secologanin biosynthesis, click here

Systematic name:

loganin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (ring-cleaving)

Comments:

A cytochrome P-450 (heme-thiolate) protein. Secologanin is the precursor of the monoterpenoid indole alkaloids and ipecac alkaloids.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 258339-71-8

References:

1.	Yamamoto, H., Katano, N., Ooi, Y. and Inoue, K. Transformation of loganin and 7-deoxyloganin into secologanin by Lonicera japonica cell suspension cultures. Phytochemistry 50 (1999) 417–422.
2.	Yamamoto, H., Katano, N., Ooi, A. and Inoue, K. Secologanin synthase which catalyzes the oxidative cleavage of loganin into secologanin is a cytochrome P-450. Phytochemistry 53 (2000) 7–12. [DOI] [PMID: 10656401]
3.	Irmler, S., Schroder, G., St-Pierre, B., Crouch, N.P., Hotze, M., Schmidt, J., Strack, D., Matern, U. and Schroder, J. Indole alkaloid biosynthesis in Catharanthus roseus: new enzyme activities and identification of cytochrome P-450 CYP72A1 as secologanin synthase. Plant J. 24 (2000) 797–804. [DOI] [PMID: 11135113]

[EC 1.14.19.62 created 2002 as EC 1.3.3.9, transferred 2018 to EC 1.14.19.62]

1.14.19.63

Accepted name:

pseudobaptigenin synthase

Reaction:

(1) calycosin + [reduced NADPH—hemoprotein reductase] + O₂ = pseudobaptigenin + [oxidized NADPH—hemoprotein reductase] + 2 H₂O
(2) pratensein + [reduced NADPH-hemoprotein reductase] + O₂ = 5-hydroxypseudobaptigenin + [oxidized NADPH—hemoprotein reductase] + 2 H₂O

Glossary:

calycosin = 3′-hydroxyformononetin
pratensein = 3′-hydroxybiochanin A

Systematic name:

calycosin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (methylenedioxy-bridge-forming)

Comments:

A cytochrome P-450 (heme-thiolate) enzyme catalysing an oxidative reaction that does not incorporate oxygen into the product. Catalyses a step in the biosynthesis of (–)-maackiain, the main pterocarpan phytoalexin in chickpea (Cicer arietinum).

Links to other databases:

References:

1.	Clemens S., Barz W. Cytochrome P₄₅₀-dependent methylenedioxy bridge formation in Cicer arietinum. Phytochemistry 41 (1996) 457–460.

[EC 1.14.19.63 created 2011 as EC 1.14.21.8, transferred 2018 to EC 1.14.19.63]

1.14.19.64

Accepted name:

(S)-stylopine synthase

Reaction:

(S)-cheilanthifoline + [reduced NADPH—hemoprotein reductase] + O₂ = (S)-stylopine + [oxidized NADPH—hemoprotein reductase] + 2 H₂O

For diagram of stylopine biosynthesis, click here

Other name(s):

(S)-cheilanthifoline oxidase (methylenedioxy-bridge-forming)

Systematic name:

(S)-cheilanthifoline,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (methylenedioxy-bridge-forming)

Comments:

A cytochrome P-450 (heme-thiolate) protein catalysing an oxidative reaction that does not incorporate oxygen into the product. Forms the second methylenedioxy bridge of the protoberberine alkaloid stylopine from oxidative ring closure of adjacent phenolic and methoxy groups of cheilanthifoline.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 138791-29-4

References:

1.	Bauer, W. and Zenk, M.H. Two methylenedioxy bridge-forming cytochrome P-450 dependent enzymes are involved in (S)-stylopine biosynthesis. Phytochemistry 30 (1991) 2953–2961.

[EC 1.14.19.64 created 1999 as EC 1.1.3.32, transferred 2002 to EC 1.14.21.1, transferred 2018 to EC 1.14.19.64]

1.14.19.65

Accepted name:

(S)-cheilanthifoline synthase

Reaction:

(S)-scoulerine + [reduced NADPH—hemoprotein reductase] + O₂ = (S)-cheilanthifoline + [oxidized NADPH—hemoprotein reductase] + 2 H₂O

For diagram of stylopine biosynthesis, click here

Other name(s):

CYP719A14 (gene name); (S)-scoulerine oxidase (methylenedioxy-bridge-forming) (ambiguous)

Systematic name:

(S)-scoulerine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase [(S)-cheilanthifoline-forming]

Comments:

A cytochrome P-450 (heme-thiolate) protein catalysing an oxidative reaction that does not incorporate oxygen into the product. Forms the methylenedioxy bridge of the protoberberine alkaloid cheilanthifoline by the oxidative ring closure of adjacent phenolic and methoxy groups of scoulerine. cf. EC 1.14.19.73, (S)-nandinine synthase, which catalyses a similar reaction at the other side of the (S)-scoulerine molecule, forming (S)-nandinine.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 138791-27-2

References:

1.	Bauer, W. and Zenk, M.H. Two methylenedioxy bridge-forming cytochrome P-450 dependent enzymes are involved in (S)-stylopine biosynthesis. Phytochemistry 30 (1991) 2953–2961.
2.	Diaz Chavez, M.L., Rolf, M., Gesell, A. and Kutchan, T.M. Characterization of two methylenedioxy bridge-forming cytochrome P450-dependent enzymes of alkaloid formation in the Mexican prickly poppy Argemone mexicana. Arch. Biochem. Biophys. 507 (2011) 186–193. [DOI] [PMID: 21094631]

[EC 1.14.19.65 created 1999 as EC 1.1.3.33, transferred 2002 to EC 1.14.21.2, modified 2016, transferred 2018 to EC 1.14.19.65]

1.14.19.66

Accepted name:

berbamunine synthase

Reaction:

(S)-N-methylcoclaurine + (R)-N-methylcoclaurine + [reduced NADPH—hemoprotein reductase] + O₂ = berbamunine + [oxidized NADPH—hemoprotein reductase] + 2 H₂O

For diagram of reaction, click here

Other name(s):

(S)-N-methylcoclaurine oxidase (C-O phenol-coupling)

Systematic name:

(S)-N-methylcoclaurine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (C-O phenol-coupling)

Comments:

A cytochrome P-450 (heme-thiolate) protein found in plants. Forms the bisbenzylisoquinoline alkaloid berbamunine by phenol oxidation of N-methylcoclaurine without the incorporation of oxygen into the product. Reaction of two molecules of (R)-N-methylcoclaurine gives the dimer guattagaumerine.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 144941-42-4

References:

1.	Stadler, R. and Zenk, M.H. The purification and characterization of a unique cytochrome P-450 enzyme from Berberis stolifera plant cell cultures. J. Biol. Chem. 268 (1993) 823–831. [PMID: 8380416]

[EC 1.14.19.66 created 1999 as EC 1.1.3.34, transferred 2002 to EC 1.14.21.3, transferred 2018 to EC 1.14.19.66]

1.14.19.67

Accepted name:

salutaridine synthase

Reaction:

(R)-reticuline + [reduced NADPH—hemoprotein reductase] + O₂ = salutaridine + [oxidized NADPH—hemoprotein reductase] + 2 H₂O

For diagram of thebaine biosynthesis, click here

Other name(s):

(R)-reticuline oxidase (C-C phenol-coupling)

Systematic name:

(R)-reticuline,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (C-C phenol-coupling)

Comments:

A cytochrome P-450 (heme-thiolate) protein found in plants. Forms the morphinan alkaloid salutaridine by intramolecular phenol oxidation of reticuline without the incorporation of oxygen into the product.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 149433-84-1

References:

1.	Gerady, R. and Zenk, M.H. Formation of salutaridine from (R)-reticuline by a membrane-bound cytochrome P-450 enzyme from Papaver somniferum. Phytochemistry 32 (1993) 79–86.

[EC 1.14.19.67 created 1999 as EC 1.1.3.35, transferred 2002 to EC 1.14.21.4, transferred 2018 to EC 1.14.19.67]

1.14.19.68

Accepted name:

(S)-canadine synthase

Reaction:

(S)-tetrahydrocolumbamine + [reduced NADPH—hemoprotein reductase] + O₂ = (S)-canadine + [oxidized NADPH—hemoprotein reductase] + 2 H₂O

For diagram of canadine biosynthesis, click here

Other name(s):

(S)-tetrahydroberberine synthase; (S)-tetrahydrocolumbamine oxidase (methylenedioxy-bridge-forming); CYP719A (gene name)

Systematic name:

(S)-tetrahydrocolumbamine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (methylenedioxy-bridge-forming)

Comments:

A cytochrome P-450 (heme-thiolate) protein found in plants. The enzyme catalyses an oxidative reaction that does not incorporate oxygen into the product. Oxidation of the methoxyphenol group of the alkaloid tetrahydrocolumbamine results in the formation of the methylenedioxy bridge of canadine.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 114308-22-4

References:

1.	Rueffer, M. and Zenk, M.H. Canadine synthase from Thalictrum tuberosum cell cultures catalyses the formation of the methylenedioxy bridge in berberine synthesis. Phytochemistry 36 (1994) 1219–1223.
2.	Ikezawa, N., Tanaka, M., Nagayoshi, M., Shinkyo, R., Sakaki, T., Inouye, K. and Sato, F. Molecular cloning and characterization of CYP719, a methylenedioxy bridge-forming enzyme that belongs to a novel P450 family, from cultured Coptis japonica cells. J. Biol. Chem. 278 (2003) 38557–38565. [PMID: 12732624]
3.	Dang, T.T. and Facchini, P.J. Cloning and characterization of canadine synthase involved in noscapine biosynthesis in opium poppy. FEBS Lett. 588 (2014) 198–204. [PMID: 24316226]

[EC 1.14.19.68 created 1999 as EC 1.1.3.36, transferred 2002 to EC 1.14.21.5, transferred 2018 to EC 1.14.19.68]

1.14.19.69

Accepted name:

biflaviolin synthase

Reaction:

(1) 2 flaviolin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = 3,3′-biflaviolin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H₂O
(2) 2 flaviolin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = 3,8′-biflaviolin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H₂O

For diagram of flaviolin metabolism, click here

Glossary:

flaviolin = 4,5,7-trihydroxynaphthalene-1,2-dione
3,3′-biflaviolin = 3,3′,6,6′,8,8′-hexahydroxy-2,2′-binaphthalene-1,1′,4,4′-tetraone
3,8′-biflaviolin = 2,3′,4,6′,7,8′-hexahydroxy-1,2′-binaphthalene-1′,4′,5,8-tetraone

Other name(s):

CYP158A2 (gene name); cytochrome P450 158A2

Systematic name:

flaviolin,reduced ferredoxin:oxygen oxidoreductase

Comments:

This cytochrome-P-450 (heme-thiolate) enzyme, from the soil-dwelling bacterium Streptomyces coelicolor A3(2), catalyses a phenol oxidation C-C coupling reaction, which results in the polymerization of flaviolin to form biflaviolin or triflaviolin without the incorporation of oxygen into the product [1,3]. The products are highly conjugated pigments that protect the bacterium from the deleterious effects of UV irradiation [1].

Links to other databases:

References:

1.	Zhao, B., Guengerich, F.P., Bellamine, A., Lamb, D.C., Izumikawa, M., Lei, L., Podust, L.M., Sundaramoorthy, M., Kalaitzis, J.A., Reddy, L.M., Kelly, S.L., Moore, B.S., Stec, D., Voehler, M., Falck, J.R., Shimada, T. and Waterman, M.R. Binding of two flaviolin substrate molecules, oxidative coupling, and crystal structure of Streptomyces coelicolor A3(2) cytochrome P450 158A2. J. Biol. Chem. 280 (2005) 11599–11607. [DOI] [PMID: 15659395]
2.	Zhao, B., Guengerich, F.P., Voehler, M. and Waterman, M.R. Role of active site water molecules and substrate hydroxyl groups in oxygen activation by cytochrome P450 158A2: a new mechanism of proton transfer. J. Biol. Chem. 280 (2005) 42188–42197. [DOI] [PMID: 16239228]
3.	Zhao, B., Lamb, D.C., Lei, L., Kelly, S.L., Yuan, H., Hachey, D.L. and Waterman, M.R. Different binding modes of two flaviolin substrate molecules in cytochrome P450 158A1 (CYP158A1) compared to CYP158A2. Biochemistry 46 (2007) 8725–8733. [DOI] [PMID: 17614370]

[EC 1.14.19.69 created 2008 as EC 1.14.21.7, transferred 2018 to EC 1.14.19.69]

1.14.19.70

Accepted name:

mycocyclosin synthase

Reaction:

cyclo(L-tyrosyl-L-tyrosyl) + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = mycocyclosin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H₂O

For diagram of cyclic dipeptide biosynthesis, click here

Glossary:

mycocyclosin = (1S,14S)-6,9-dihydroxy-15,17-diazatetracyclo[12.2.2.1^3,7.1^8,12]icosa-3(20),4,6,8(19),9,11-hexaene-16,18-dione

Other name(s):

CYP121; rv2276 (locus name)

Systematic name:

cyclo(L-tyrosyl-L-tyrosyl),reduced ferredoxin:oxygen oxidoreductase (diarylbridge-forming)

Comments:

A cytochrome P-450 (heme-thiolate) protein from the bacterium Mycobacterium tuberculosis catalysing an oxidative reaction that does not incorporate oxygen into the product.

Links to other databases:

References:

Belin, P., Le Du, M.H., Fielding, A., Lequin, O., Jacquet, M., Charbonnier, J.B., Lecoq, A., Thai, R., Courcon, M., Masson, C., Dugave, C., Genet, R., Pernodet, J.L. and Gondry, M. Identification and structural basis of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 106 (2009) 7426–7431. [DOI] [PMID: 19416919]

[EC 1.14.19.70 created 2013 as EC 1.14.21.9, transferred 2018 to EC 1.14.19.70]

1.14.19.71

Accepted name:

fumitremorgin C synthase

Reaction:

tryprostatin A + [reduced NADPH—hemoprotein reductase] + O₂ = fumitremorgin C + [oxidized NADPH—hemoprotein reductase] + 2 H₂O

For diagram of fumitremorgin alkaloid biosynthesis (part 1), click here

Glossary:

tryprostatin A = (3S,8aS)-3-{[6-methoxy-2-(3-methylbut-2-en-1-yl)-1H-indol-3-yl]methyl}hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
fumitremorgin C = (5aS,12S,14aS)-9-methoxy-12-(2-methylprop-1-en-1-yl)-1,2,3,5a,6,11,12,14a-octahydro-5H,14H-pyrrolo[1′′,2′′:4′,5′]pyrazino[1′,2′:1,6]pyrido[3,4-b]indole-5,14-dione

Other name(s):

ftmE (gene name)

Systematic name:

tryprostatin A,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase

Comments:

A cytochrome P-450 (heme-thiolate) protein. The protein from the fungus Aspergillus fumigatus also has activity with tryprostatin B forming demethoxyfumitremorgin C. Involved in the biosynthetic pathways of several indole alkaloids such as fumitremorgins and verruculogen.

Links to other databases:

References:

1.	Kato, N., Suzuki, H., Takagi, H., Asami, Y., Kakeya, H., Uramoto, M., Usui, T., Takahashi, S., Sugimoto, Y. and Osada, H. Identification of cytochrome P450s required for fumitremorgin biosynthesis in Aspergillus fumigatus. ChemBioChem 10 (2009) 920–928. [DOI] [PMID: 19226505]

[EC 1.14.19.71 created 2013 as EC 1.14.21.10, transferred 2018 to EC 1.14.19.71]

1.14.19.72

Accepted name:

(–)-pluviatolide synthase

Reaction:

(–)-matairesinol + [reduced NADPH—hemoprotein reductase] + O₂ = (–)-pluviatolide + [oxidized NADPH—hemoprotein reductase] + 2 H₂O

For diagram of podophyllotoxin biosynthesis, click here

Glossary:

(–)-matairesinol = 3R,4R)-3,4-bis[(4-hydroxy-3-methoxyphenyl)methyl]oxolan-2-one
(–)-pluviatolide = ((3R,4R)-4-(2H-1,3-benzodioxol-5-ylmethyl)-3-[(4-hydroxy-3-methoxyphenyl)methyl]oxolan-2-one

Other name(s):

CYP719A23 (gene name)

Systematic name:

(–)-matairesinol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (methylenedioxy-bridge-forming)

Comments:

A cytochrome P-450 (heme-thiolate) protein. The enzyme from the plants Sinopodophyllum hexandrum and Podophyllum peltatum catalyses the formation of a methylenedioxy-bridge. It is involved in the biosynthesis of podophyllotoxin, a non-alkaloid toxin lignan whose derivatives are important anticancer drugs.

Links to other databases:

References:

1.	Marques, J.V., Kim, K.W., Lee, C., Costa, M.A., May, G.D., Crow, J.A., Davin, L.B. and Lewis, N.G. Next generation sequencing in predicting gene function in podophyllotoxin biosynthesis. J. Biol. Chem. 288 (2013) 466–479. [DOI] [PMID: 23161544]

[EC 1.14.19.72 created 2016 as EC 1.14.21.11, transferred 2018 to EC 1.14.19.72]

1.14.19.73

Accepted name:

(S)-nandinine synthase

Reaction:

(S)-scoulerine + [reduced NADPH—hemoprotein reductase] + O₂ = (S)-nandinine + [oxidized NADPH—hemoprotein reductase] + 2 H₂O

For diagram of nandinine biosynthesis, click here

Glossary:

(S)-scoulerine = (13aS)-3,10-dimethoxy-5,8,13,13a-tetrahydro-6H-isoquino[3,2-a]isoquinoline-2,9-diol
(S)-cheilanthifoline = (6aS)-9-methoxy-6,11,12,14-tetrahydro-2H,6aH-[1,3]dioxolo[4,5-h]isoquino[2,1-b]isoquinolin-8-ol

Other name(s):

CYP719A3

Systematic name:

(S)-scoulerine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase [(S)-nandinine-forming]

Comments:

A cytochrome P-450 (heme-thiolate) enzyme found in plants. The enzyme catalyses an oxidative reaction that does not incorporate oxygen into the product. Forms the methylenedioxy bridge of the protoberberine alkaloid (S)-nandinine by the oxidative ring closure of adjacent phenolic and methoxy groups of (S)-scoulerine. cf. EC 1.14.19.65, (S)-cheilanthifoline synthase, which catalyses a similar reaction at the other side of the (S)-scoulerine molecule, forming (S)-cheilanthifoline.

Links to other databases:

References:

1.	Ikezawa, N., Iwasa, K. and Sato, F. Molecular cloning and characterization of methylenedioxy bridge-forming enzymes involved in stylopine biosynthesis in Eschscholzia californica. FEBS J. 274 (2007) 1019–1035. [DOI] [PMID: 17250743]
2.	Diaz Chavez, M.L., Rolf, M., Gesell, A. and Kutchan, T.M. Characterization of two methylenedioxy bridge-forming cytochrome P450-dependent enzymes of alkaloid formation in the Mexican prickly poppy Argemone mexicana. Arch. Biochem. Biophys. 507 (2011) 186–193. [DOI] [PMID: 21094631]

[EC 1.14.19.73 created 2016 as EC 1.14.21.12, transferred 2018 to EC 1.14.19.73]

1.14.19.74

Accepted name:

(+)-piperitol/(+)-sesamin synthase

Reaction:

(1) (+)-pinoresinol + [reduced NADPH-hemoprotein reductase] + O₂ = (+)-piperitol + [oxidized NADPH-hemoprotein reductase] + 2 H₂O
(2) (+)-piperitol + [reduced NADPH-hemoprotein reductase] + O₂ = (+)-sesamin + [oxidized NADPH-hemoprotein reductase] + 2 H₂O

For diagram of sesamin biosynthesis, click here

Other name(s):

CYP81Q1; CYP81Q2; PS; PSS; SS; piperitol synthase; sesamin synthase

Systematic name:

(+)-pinoresinol,[reduced NADPH-hemoprotein reductase]:oxygen oxidoreductase (cyclizing)

Comments:

A cytochrome P-450 (heme-thiolate) protein. Isolated from Sesamum indicum (sesame) and S. radiatum (black sesame).

Links to other databases:

References:

Ono, E., Nakai, M., Fukui, Y., Tomimori, N., Fukuchi-Mizutani, M., Saito, M., Satake, H., Tanaka, T., Katsuta, M., Umezawa, T. and Tanaka, Y. Formation of two methylenedioxy bridges by a Sesamum CYP81Q protein yielding a furofuran lignan, (+)-sesamin. Proc. Natl. Acad. Sci. USA 103 (2006) 10116–10121. [PMID: 16785429]

[EC 1.14.19.74 created 2018]

1.14.20.14

Accepted name:

hapalindole-type alkaloid chlorinase

Reaction:

(1) hapalindole U + 2-oxoglutarate + O₂ + chloride = hapalindole G + succinate + CO₂ + H₂O
(2)12-epi-fischerindole U + 2-oxoglutarate + O₂ + chloride = 12-epi-fischerindole G + succinate + CO₂ + H₂O

For diagram of hapalindole/fischerindole biosynthesis, click here

Glossary:

12-epi-fischerindole U = (6aS,9S,10R,10aS)-9-ethenyl-10-isocyano-6,6,9-trimethyl-5,6,6a,7,8,9,10,10a-octahydroindeno[2,1-b]indole
12-epi-fischerindole G = (6aR,8R,9S,10R,10aS)-8-chloro-9-ethenyl-10-isocyano-6,6,9-trimethyl-5,6,6a,7,8,9,10,10a-octahydroindeno[2,1-b]indole

Other name(s):

ambO5 (gene name); welO5 (gene name)

Systematic name:

12-epi-fischerindole U,2-oxoglutarate:oxygen oxidoreductase (13-halogenating)

Comments:

The enzyme, characterized from hapalindole-type alkaloids-producing cyanobacteria, is a specialized iron(II)/2-oxoglutarate-dependent oxygenase that catalyses the chlorination of its substrates in a reaction that requires oxygen, chloride ions, iron(II) and 2-oxoglutarate.

Links to other databases:

References:

1.	Hillwig, M.L. and Liu, X. A new family of iron-dependent halogenases acts on freestanding substrates. Nat. Chem. Biol. 10 (2014) 921–923. [PMID: 25218740]
2.	Zhu, Q., Hillwig, M.L., Doi, Y. and Liu, X. Aliphatic halogenase enables late-stage C-H functionalization: selective synthesis of a brominated fischerindole alkaloid with enhanced antibacterial activity. ChemBioChem 17 (2016) 466–470. [PMID: 26749394]
3.	Hillwig, M.L., Zhu, Q., Ittiamornkul, K. and Liu, X. Discovery of a promiscuous non-heme iron halogenase in ambiguine alkaloid biogenesis: implication for an evolvable enzyme family for late-stage halogenation of aliphatic carbons in small molecules. Angew. Chem. Int. Ed. Engl. 55 (2016) 5780–5784. [PMID: 27027281]

[EC 1.14.20.14 created 2018]

1.14.20.15

Accepted name:

L-threonyl-[L-threonyl-carrier protein] 4-chlorinase

Reaction:

an L-threonyl-[L-threonyl-carrier protein] + 2-oxoglutarate + O₂ + Cl^- = a 4-chloro-L-threonyl-[L-threonyl-carrier protein] + succinate + CO₂ + H₂O

Other name(s):

syrB2 (gene name)

Systematic name:

L-threonyl-[L-threonyl-carrier protein],2-oxoglutarate:oxygen oxidoreductase (4-halogenating)

Comments:

The enzyme, characterized from the bacterium Pseudomonas syringae, participates in syringomycin E biosynthesis. The enzyme is a specialized iron(II)/2-oxoglutarate-dependent oxygenase that catalyses the chlorination of its substrate in a reaction that requires oxygen, chloride ions, ferrous iron and 2-oxoglutarate.

Links to other databases:

References:

1.	Vaillancourt, F.H., Yin, J. and Walsh, C.T. SyrB2 in syringomycin E biosynthesis is a nonheme Fe^II α-ketoglutarate- and O₂-dependent halogenase. Proc. Natl. Acad. Sci. USA 102 (2005) 10111–10116. [DOI] [PMID: 16002467]

[EC 1.14.20.15 created 2018]

1.14.21.1

Transferred entry:

(S)-stylopine synthase. Now EC 1.14.19.64, (S)-stylopine synthase

[EC 1.14.21.1 created 2002, deleted 2018]

1.14.21.2

Transferred entry:

(S)-cheilanthifoline synthase. Now EC 1.14.19.65, (S)-cheilanthifoline synthase

[EC 1.14.21.2 created 2002, modified 2016, deleted 2018]

1.14.21.3

Transferred entry:

berbamunine synthase. Now EC 1.14.19.66, berbamunine synthase

[EC 1.14.21.3 created 2002, deleted 2018]

1.14.21.4

Transferred entry:

salutaridine synthase. Now EC 1.14.19.67, salutaridine synthase

[EC 1.14.21.4 created 2002, deleted 2018]

1.14.21.5

Transferred entry:

(S)-canadine synthase. Now EC 1.14.19.68, (S)-canadine synthase

[EC 1.14.21.5 created 2002, deleted 2018]

1.14.21.7

Transferred entry:

biflaviolin synthase. Now EC 1.14.19.69, biflaviolin synthase

[EC 1.14.21.7 created 2008, deleted 2018]

1.14.21.8

Transferred entry:

pseudobaptigenin synthase. Now EC 1.14.19.63, pseudobaptigenin synthase.

[EC 1.14.21.8 created 2011, deleted 2018]

1.14.21.9

Transferred entry:

mycocyclosin synthase. Now EC 1.14.19.70, mycocyclosin synthase

[EC 1.14.21.9 created 2013, deleted 2018]

1.14.21.10

Transferred entry:

fumitremorgin C synthase. Now EC 1.14.19.71, fumitremorgin C synthase

[EC 1.14.21.10 created 2013, deleted 2018]

1.14.21.11

Transferred entry:

(–)-pluviatolide synthase. Now EC 1.14.19.72, (–)-pluviatolide synthase

[EC 1.14.21.11 created 2016, deleted 2018]

1.14.21.12

Transferred entry:

(S)-nandinine synthase. Now EC 1.14.19.73, (S)-nandinine synthase

[EC 1.14.21.12 created 2016, deleted 2018]

1.14.99.43

Transferred entry:

β-amyrin 24-hydroxylase. Now EC 1.14.14.134, β-amyrin 24-hydroxylase

[EC 1.14.99.43 created 2011, deleted 2018]

1.14.99.45

Transferred entry:

carotene ε-monooxygenase. Now EC 1.14.14.158, carotene ε-monooxygenase

[EC 1.14.99.45 created 2011, deleted 2018]

1.14.99.49

Transferred entry:

2-hydroxy-5-methyl-1-naphthoate 7-hydroxylase. Now EC 1.14.15.31, 2-hydroxy-5-methyl-1-naphthoate 7-hydroxylase

[EC 1.14.99.49 created 2014, deleted 2018]

1.14.99.61

Accepted name:

cyclooctat-9-en-7-ol 5-monooxygenase

Reaction:

cyclooctat-9-en-7-ol + reduced acceptor + O₂ = cyclooctat-9-ene-5,7-diol + acceptor + H₂O

For diagram of cyclooctatin biosynthesis, click here

Glossary:

cyclooctat-9-en-7-ol = (1S,3aS,4R,7S,9aS,10aS)-1,4,9a-trimethyl-7-(propan-2-yl)-1,2,3,3a,4,5,7,8,9,9a,10,10a-dodecahydrodicyclopenta[a,d][8]annulen-4-ol
cyclooctat-9-ene-5,7-diol = (1S,3R,3aS,4R,7S,9aS,10aS)-1,4,9a-trimethyl-7-(propan-2-yl)-1,2,3,3a,4,5,7,8,9,9a,10,10a-dodecahydrodicyclopenta[a,d][8]annulene-3,4-diol

Other name(s):

CotB3

Systematic name:

cyclooctat-9-en-7-ol,hydrogen-donor:oxygen oxidoreductase (5-hydroxylating)

Comments:

Isolated from the bacterium Streptomyces melanosporofaciens M1614-43f2. Involved in the biosynthesis of cyclooctatin.

Links to other databases:

References:

1.	Kim, S.Y., Zhao, P., Igarashi, M., Sawa, R., Tomita, T., Nishiyama, M. and Kuzuyama, T. Cloning and heterologous expression of the cyclooctatin biosynthetic gene cluster afford a diterpene cyclase and two P450 hydroxylases. Chem. Biol. 16 (2009) 736–743. [DOI] [PMID: 19635410]
2.	Gorner, C., Schrepfer, P., Redai, V., Wallrapp, F., Loll, B., Eisenreich, W., Haslbeck, M. and Bruck, T. Identification, characterization and molecular adaptation of class I redox systems for the production of hydroxylated diterpenoids. Microb. Cell Fact. 15:86 (2016). [PMID: 27216162]

[EC 1.14.99.61 created 2018]

1.14.99.62

Accepted name:

cyclooctatin synthase

Reaction:

cyclooctat-9-ene-5,7-diol + reduced acceptor + O₂ = cyclooctatin + acceptor + H₂O

For diagram of cyclooctatin biosynthesis, click here

Glossary:

cyclooctat-9-ene-5,7-diol = (1S,3R,3aS,4R,7S,9aS,10aS)-1,4,9a-trimethyl-7-(propan-2-yl)-1,2,3,3a,4,5,7,8,9,9a,10,10a-dodecahydrodicyclopenta[a,d][8]annulene-3,4-diol
cyclooctatin = cycloctat-9-ene-5,7,18-triol = (1R,3R,3aS,4R,7S,9aS,10aS)-1-(hydroxymethyl-)4,9a-dimethyl-7-(propan-2-yl)-1,2,3,3a,4,5,7,8,9,9a,10,10a-dodecahydrodicyclopenta[a,d][8]annulene-3,4-diol

Other name(s):

CotB4

Systematic name:

cyclooctat-9-ene-5,7-diol,hydrogen-donor:oxygen oxidoreductase (18-hydroxylating)

Comments:

Isolated from the bacterium Streptomyces melanosporofaciens M1614-43f2.

Links to other databases:

References:

1.	Kim, S.Y., Zhao, P., Igarashi, M., Sawa, R., Tomita, T., Nishiyama, M. and Kuzuyama, T. Cloning and heterologous expression of the cyclooctatin biosynthetic gene cluster afford a diterpene cyclase and two P450 hydroxylases. Chem. Biol. 16 (2009) 736–743. [DOI] [PMID: 19635410]
2.	Gorner, C., Schrepfer, P., Redai, V., Wallrapp, F., Loll, B., Eisenreich, W., Haslbeck, M. and Bruck, T. Identification, characterization and molecular adaptation of class I redox systems for the production of hydroxylated diterpenoids. Microb. Cell Fact. 15:86 (2016). [PMID: 27216162]

[EC 1.14.99.62 created 2018]

1.14.99.63

Accepted name:

β-carotene 4-ketolase

Reaction:

(1) β-carotene + 2 reduced acceptor + 2 O₂ = echinenone + 2 acceptor + 3 H₂O
(2) echinenone + 2 reduced acceptor + 2 O₂ = canthaxanthin + 2 acceptor + 3 H₂O

For diagram of canthaxanthin biosynthesis, click here

Glossary:

echinenone = β,β-caroten-4-one
canthaxanthin = β,β-carotene-4,4′-dione
zeaxanthin = β,β-carotene-3,3′-diol
astaxanthin = 3,3′-dihydroxy-β,β-carotene-4,4′-dione

Other name(s):

BKT (ambiguous); β-C-4 oxygenase; β-carotene ketolase; crtS (gene name); crtW (gene name)

Systematic name:

β-carotene,donor:oxygen oxidoreductase (echinenone-forming)

Comments:

The enzyme, studied from algae, plants, fungi, and bacteria, adds an oxo group at position 4 of a carotenoid β ring. It is involved in the biosynthesis of carotenoids such as astaxanthin and flexixanthin. The enzyme does not act on β rings that are hydroxylated at position 3, such as in zeaxanthin (cf. EC 1.14.99.64, zeaxanthin 4-ketolase). The enzyme from the yeast Xanthophyllomyces dendrorhous is bifuntional and also catalyses the activity of EC 1.14.15.24, β-carotene 3-hydroxylase.

Links to other databases:

References:

1.	Lotan, T. and Hirschberg, J. Cloning and expression in Escherichia coli of the gene encoding β-C-4-oxygenase, that converts β-carotene to the ketocarotenoid canthaxanthin in Haematococcus pluvialis. FEBS Lett. 364 (1995) 125–128. [PMID: 7750556]
2.	Breitenbach, J., Misawa, N., Kajiwara, S. and Sandmann, G. Expression in Escherichia coli and properties of the carotene ketolase from Haematococcus pluvialis. FEMS Microbiol. Lett. 140 (1996) 241–246. [PMID: 8764486]
3.	Steiger, S. and Sandmann, G. Cloning of two carotenoid ketolase genes from Nostoc punctiforme for the heterologous production of canthaxanthin and astaxanthin. Biotechnol. Lett. 26 (2004) 813–817. [PMID: 15269553]
4.	Ojima, K., Breitenbach, J., Visser, H., Setoguchi, Y., Tabata, K., Hoshino, T., van den Berg, J. and Sandmann, G. Cloning of the astaxanthin synthase gene from Xanthophyllomyces dendrorhous (Phaffia rhodozyma) and its assignment as a β-carotene 3-hydroxylase/4-ketolase. Mol. Genet. Genomics 275 (2006) 148–158. [PMID: 16416328]
5.	Tao, L., Yao, H., Kasai, H., Misawa, N. and Cheng, Q. A carotenoid synthesis gene cluster from Algoriphagus sp. KK10202C with a novel fusion-type lycopene β-cyclase gene. Mol. Genet. Genomics 276 (2006) 79–86. [PMID: 16625353]
6.	Kathiresan, S., Chandrashekar, A., Ravishankar, G.A. and Sarada, R. Regulation of astaxanthin and its intermediates through cloning and genetic transformation of β-carotene ketolase in Haematococcus pluvialis. J. Biotechnol. 196-197 (2015) 33–41. [PMID: 25612872]

[EC 1.14.99.63 created 2018]

1.14.99.64

Accepted name:

zeaxanthin 4-ketolase

Reaction:

(1) zeaxanthin + 2 reduced acceptor + 2 O₂ = adonixanthin + 2 acceptor + 3 H₂O
(2) adonixanthin + 2 reduced acceptor + 2 O₂ = (3S,3′S)-astaxanthin + 2 acceptor + 3 H₂O

For diagram of astaxanthin biosynthesis, click here

Glossary:

zeaxanthin = β,β-carotene-3,3′-diol
adonixanthin = 3,3′-dihydroxy-β,β-carotene-4-one
(3S,3′S)-astaxanthin = (3S,3′S)-3,3′-dihydroxy-β,β-carotene-4,4′-dione

Other name(s):

BKT (ambiguous); crtW148 (gene name)

Systematic name:

zeaxanthin,donor:oxygen oxidoreductase (adonixanthin-forming)

Comments:

The enzyme has a similar activity to that of EC 1.14.99.63, β-carotene 4-ketolase, but unlike that enzyme is able to also act on zeaxanthin.

Links to other databases:

References:

1.	Zhong, Y.J., Huang, J.C., Liu, J., Li, Y., Jiang, Y., Xu, Z.F., Sandmann, G. and Chen, F. Functional characterization of various algal carotenoid ketolases reveals that ketolating zeaxanthin efficiently is essential for high production of astaxanthin in transgenic Arabidopsis. J. Exp. Bot. 62 (2011) 3659–3669. [PMID: 21398427]
2.	Huang, J., Zhong, Y., Sandmann, G., Liu, J. and Chen, F. Cloning and selection of carotenoid ketolase genes for the engineering of high-yield astaxanthin in plants. Planta 236 (2012) 691–699. [PMID: 22526507]

[EC 1.14.99.64 created 2018]

1.17 Acting on CH or CH₂ groups

1.17.9 With a copper protein as acceptor

1.17.9.1

Accepted name:

4-methylphenol dehydrogenase (hydroxylating)

Reaction:

4-methylphenol + 4 oxidized azurin + H₂O = 4-hydroxybenzaldehyde + 4 reduced azurin + 4 H⁺ (overall reaction)
(1a) 4-methylphenol + 2 oxidized azurin + H₂O = 4-hydroxybenzyl alcohol + 2 reduced azurin + 2 H⁺
(1b) 4-hydroxybenzyl alcohol + 2 oxidized azurin = 4-hydroxybenzaldehyde + 2 reduced azurin + 2 H⁺

Glossary:

4-methylphenol = 4-cresol = p-cresol

Other name(s):

pchCF (gene names); p-cresol-(acceptor) oxidoreductase (hydroxylating); p-cresol methylhydroxylase; 4-cresol dehydrogenase (hydroxylating)

Systematic name:

4-methylphenol:oxidized azurin oxidoreductase (methyl-hydroxylating)

Comments:

This bacterial enzyme contains a flavin (FAD) subunit and a cytochrome c subunit. The flavin subunit abstracts two hydrogen atoms from the substrate, forming a quinone methide intermediate, then hydrates the latter at the benzylic carbon with a hydroxyl group derived from water. The protons are lost to the bulk solvent, while the electrons are passed to the heme on the cytochrome subunit, and from there to azurin, a small copper-binding protein that is co-localized with the enzyme in the periplasm. The first hydroxylation forms 4-hydroxybenzyl alcohol; a second hydroxylation converts this into 4-hydroxybenzaldehyde.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, KEGG, PDB, CAS registry number: 66772-07-4

References:

1.	Hopper, D.J. and Taylor, D.G. The purification and properties of p-cresol-(acceptor) oxidoreductase (hydroxylating), a flavocytochrome from Pseudomonas putida. Biochem. J. 167 (1977) 155–162. [PMID: 588247]
2.	McIntire, W., Edmondson, D.E. and Singer, T.P. 8α-O-Tyrosyl-FAD: a new form of covalently bound flavin from p-cresol methylhydroxylase. J. Biol. Chem. 255 (1980) 6553–6555. [PMID: 7391034]
3.	Hopper, D.J., Jones, M.R. and Causer, M.J. Periplasmic location of p-cresol methylhydroxylase in Pseudomonas putida. FEBS Lett. 182 (1985) 485–488. [PMID: 3920077]
4.	Bossert, I.D., Whited, G., Gibson, D.T. and Young, L.Y. Anaerobic oxidation of p-cresol mediated by a partially purified methylhydroxylase from a denitrifying bacterium. J. Bacteriol. 171 (1989) 2956–2962. [DOI] [PMID: 2722739]
5.	Reeve, C.D., Carver, M.A. and Hopper, D.J. Stereochemical aspects of the oxidation of 4-ethylphenol by the bacterial enzyme 4-ethylphenol methylenehydroxylase. Biochem. J. 269 (1990) 815–819. [PMID: 1697166]
6.	Peters, F., Heintz, D., Johannes, J., van Dorsselaer, A. and Boll, M. Genes, enzymes, and regulation of para-cresol metabolism in Geobacter metallireducens. J. Bacteriol. 189 (2007) 4729–4738. [PMID: 17449613]
7.	Johannes, J., Bluschke, A., Jehmlich, N., von Bergen, M. and Boll, M. Purification and characterization of active-site components of the putative p-cresol methylhydroxylase membrane complex from Geobacter metallireducens. J. Bacteriol. 190 (2008) 6493–6500. [PMID: 18658262]

[EC 1.17.9.1 created 1983 as EC 1.17.99.1, modified 2001, modified 2011, modified 2015, transferred 2018 to EC 1.17.9.1]

1.17.99.1

Transferred entry:

4-methylphenol dehydrogenase (hydroxylating). Now EC 1.17.9.1, 4-methylphenol dehydrogenase (hydroxylating)

[EC 1.17.99.1 created 1983, modified 2001, modified 2011, modified 2015, deleted 2018]

1.18.1.8

Transferred entry:

ferredoxin-NAD⁺ oxidoreductase (Na⁺-transporting). Now EC 7.2.1.2, ferredoxin—NAD⁺ oxidoreductase (Na⁺-transporting)

[EC 1.18.1.8 created 2015, deleted 2018]

1.21.98.4

Accepted name:

PqqA peptide cyclase

Reaction:

a PqqA peptide + S-adenosyl-L-methionine = a PqqA peptide with linked Glu-Tyr residues + 5′-deoxyadenosine + L-methionine

Glossary:

PqqA peptide = pyrroloquinoline quinone biosynthesis protein A, a small peptide that provides the precursor for the biosynthesis of the cofactor pyrroloquinoline quinone

Other name(s):

pqqE (gene name)

Systematic name:

PqqA peptide:S-adenosyl-L-methionine oxidoreductase (cyclizing)

Comments:

This bacterial enzyme, which is a member of the radical SAM protein family, catalyses the formation of a C-C bond between C-4 of glutamate and C-3 of tyrosine residues of the PqqA protein (which are separated by three amino acid residues). This is the first enzymic step in the biosynthesis of the bacterial enzyme cofactor pyrroloquinoline quinone (PQQ). The reaction is dependent on the presence of a reductant (flavodoxin) and the accessory protein PqqD.

Links to other databases:

References:

1.	Wecksler, S.R., Stoll, S., Iavarone, A.T., Imsand, E.M., Tran, H., Britt, R.D. and Klinman, J.P. Interaction of PqqE and PqqD in the pyrroloquinoline quinone (PQQ) biosynthetic pathway links PqqD to the radical SAM superfamily. Chem. Commun. (Camb.) 46 (2010) 7031–7033. [PMID: 20737074]
2.	Latham, J.A., Iavarone, A.T., Barr, I., Juthani, P.V. and Klinman, J.P. PqqD is a novel peptide chaperone that forms a ternary complex with the radical S-adenosylmethionine protein PqqE in the pyrroloquinoline quinone biosynthetic pathway. J. Biol. Chem. 290 (2015) 12908–12918. [PMID: 25817994]
3.	Barr, I., Latham, J.A., Iavarone, A.T., Chantarojsiri, T., Hwang, J.D. and Klinman, J.P. Demonstration that the radical S-adenosylmethionine (SAM) enzyme PqqE catalyzes de novo carbon-carbon cross-linking within a peptide substrate PqqA in the presence of the peptide chaperone PqqD. J. Biol. Chem. 291 (2016) 8877–8884. [PMID: 26961875]

[EC 1.21.98.4 created 2018]

2.1.1.349

Accepted name:

toxoflavin synthase

Reaction:

(1) S-adenosyl-L-methionine + 1,6-didemethyltoxoflavin = S-adenosyl-L-homocysteine + reumycin
(2) S-adenosyl-L-methionine + reumycin = S-adenosyl-L-homocysteine + toxoflavin

For diagram of toxoflavin biosynthesis, click here

Glossary:

reumycin = 1-demethyltoxoflavin
toxoflavin = 1,6-dimethylpyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione

Other name(s):

toxA (gene name)

Systematic name:

S-adenosyl-L-methionine:1,6-didemethyltoxoflavin N¹,N⁶-dimethyltransferase (toxoflavin-forming)

Comments:

The enzyme is a dual-specificity methyltransferase that catalyses the last two steps of toxoflavin biosynthesis. Toxoflavin is a major virulence factor of several bacterial crop pathogens.

Links to other databases:

References:

1.	Fenwick, M.K., Philmus, B., Begley, T.P. and Ealick, S.E. Burkholderia glumae ToxA Is a dual-specificity methyltransferase that catalyzes the last two steps of toxoflavin biosynthesis. Biochemistry 55 (2016) 2748–2759. [PMID: 27070241]

[EC 2.1.1.349 created 2018]

2.3.1.273

Accepted name:

diglucosylglycerate octanoyltransferase

Reaction:

octanoyl-CoA + 2-O-[α-D-glucopyranosyl-(1→6)-α-D-glucopyranosyl]-D-glycerate = CoA + 2-O-[6-O-octanoyl-α-D-glucopyranosyl-(1→6)-α-D-glucopyranosyl]-D-glycerate

Other name(s):

octT (gene name); DGG octanoyltransferase

Systematic name:

octanoyl-CoA:2-O-[α-D-glucopyranosyl-(1→6)-α-D-glucopyranosyl]-D-glycerate octanoyltransferase

Comments:

The enzyme, characterized from mycobacteria, is involved in the biosynthesis of methylglucose lipopolysaccharide (MGLP). The enzyme can also act on 2-O-(α-D-glucopyranosyl)-D-glycerate, but with lower activity.

Links to other databases:

References:

Maranha, A., Moynihan, P.J., Miranda, V., Correia Lourenco, E., Nunes-Costa, D., Fraga, J.S., Jose Barbosa Pereira, P., Macedo-Ribeiro, S., Ventura, M.R., Clarke, A.J. and Empadinhas, N. Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharides. Sci. Rep. 5:13610 (2015). [PMID: 26324178]

[EC 2.3.1.273 created 2018]

2.4.1.358

Accepted name:

acylphloroglucinol glucosyltransferase

Reaction:

UDP-α-D-glucose + 2-acylphloroglucinol = UDP + 2-acylphloroglucinol 1-O-β-D-glucoside

For diagram of phloroisovalerophenone 2-o-glucoside biosynthesis, click here

Glossary:

phlorisobutyrophenone = 2-methyl-1-(2,4,6-trihydroxyphenyl)propan-1-one
phlorisovalerophenone = 3-methyl-1-(2,4,6-trihydroxyphenyl)butan-1-one

Other name(s):

UGT71K3

Systematic name:

UDP-α-D-glucose:2-acylphloroglucinol 1-O-β-glucosyltransferase

Comments:

Isolated from strawberries (Fragaria X ananassa). Acts best on phloroisovalerophenone and phlorobutyrophenone but will also glycosylate many other phenolic compounds. A minor product of the reaction is the 5-O-β-D-glucoside.

Links to other databases:

References:

1.	Song, C., Zhao, S., Hong, X., Liu, J., Schulenburg, K. and Schwab, W. A UDP-glucosyltransferase functions in both acylphloroglucinol glucoside and anthocyanin biosynthesis in strawberry (Fragaria x ananassa). Plant J. 85 (2016) 730–742. [PMID: 26859691]

[EC 2.4.1.358 created 2018]

*EC

2.5.1.17

Accepted name:

corrinoid adenosyltransferase

Reaction:

(1) 2 ATP + 2 cob(II)alamin + a reduced flavoprotein = 2 triphosphate + 2 adenosylcob(III)alamin + an oxidized flavoprotein (overall reaction)
(1a) 2 cob(II)alamin + 2 [corrinoid adenosyltransferase] = 2 [corrinoid adenosyltransferase]-cob(II)alamin
(1b) a reduced flavoprotein + 2 [corrinoid adenosyltransferase]-cob(II)alamin = an oxidized flavoprotein + 2 [corrinoid adenosyltransferase]-cob(I)alamin (spontaneous)
(1c) 2 ATP + 2 [corrinoid adenosyltransferase]-cob(I)alamin = 2 triphosphate + 2 adenosylcob(III)alamin + 2 [corrinoid adenosyltransferase]
(2) 2 ATP + 2 cob(II)yrinic acid a,c-diamide + a reduced flavoprotein = 2 triphosphate + 2 adenosylcob(III)yrinic acid a,c-diamide + an oxidized flavoprotein (overall reaction)
(2a) 2 cob(II)yrinic acid a,c-diamide + 2 [corrinoid adenosyltransferase] = 2 [corrinoid adenosyltransferase]-cob(II)yrinic acid a,c-diamide
(2b) a reduced flavoprotein + 2 [corrinoid adenosyltransferase]-cob(II)yrinic acid a,c-diamide = an oxidized flavoprotein + 2 [corrinoid adenosyltransferase]-cob(I)yrinic acid a,c-diamide (spontaneous)
(2c) 2 ATP + 2 [corrinoid adenosyltransferase]-cob(I)yrinic acid a,c-diamide = 2 triphosphate + 2 adenosylcob(III)yrinic acid a,c-diamide + 2 [corrinoid adenosyltransferase]

For diagram of corrin biosynthesis (part 5), click here and for diagram of the cobinamide salvage pathways, click here

Other name(s):

MMAB (gene name); cobA (gene name); cobO (gene name); pduO (gene name); ATP:corrinoid adenosyltransferase; cob(I)alamin adenosyltransferase; aquacob(I)alamin adenosyltransferase; aquocob(I)alamin vitamin B_12s adenosyltransferase; ATP:cob(I)alamin Coβ-adenosyltransferase; ATP:cob(I)yrinic acid-a,c-diamide Coβ-adenosyltransferase; cob(I)yrinic acid a,c-diamide adenosyltransferase

Systematic name:

ATP:cob(II)alamin Coβ-adenosyltransferase

Comments:

The corrinoid adenosylation pathway comprises three steps: (i) reduction of Co(III) within the corrinoid to Co(II) by a one-electron transfer. This can occur non-enzymically in the presence of dihydroflavin nucleotides or reduced flavoproteins [3]. (ii) Co(II) is bound by corrinoid adenosyltransferase, resulting in displacement of the lower axial ligand by an aromatic residue. The reduction potential of the 4-coordinate Co(II) intermediate is raised by ~250 mV compared with the free compound, bringing it to within physiological range. This is followed by a second single-electron transfer from either free dihydroflavins or the reduced flavin cofactor of flavoproteins, resulting in reduction to Co(I) [7]. (iii) the Co(I) conducts a nucleophilic attack on the adenosyl moiety of ATP, resulting in transfer of the deoxyadenosyl group and oxidation of the cobalt atom to Co(III) state. Three types of corrinoid adenosyltransferases, not related by sequence, have been described. In the anaerobic bacterium Salmonella enterica they are encoded by the cobA gene (a housekeeping enzyme involved in both the de novo biosynthesis and the salvage of adenosylcobalamin), the pduO gene (involved in (S)-propane-1,2-diol utilization), and the eutT gene (involved in ethanolamine utilization). Since EutT hydrolyses triphosphate to diphosphate and phosphate during catalysis, it is classified as a separate enzyme. The mammalian enzyme belongs to the PduO type. The enzyme can act on other corrinoids, such as cob(II)inamide.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 37277-84-2

References:

1.	Vitols, E., Walker, G.A. and Huennekens, F.M. Enzymatic conversion of vitamin B_12s to a cobamide coenzyme, α-(5,6-dimethylbenzimidazolyl)deoxyadenosylcobamide (adenosyl-B₁₂). J. Biol. Chem. 241 (1966) 1455–1461. [PMID: 5946606]
2.	Bauer, C.B., Fonseca, M.V., Holden, H.M., Thoden, J.B., Thompson, T.B., Escalante-Semerena, J.C. and Rayment, I. Three-dimensional structure of ATP:corrinoid adenosyltransferase from Salmonella typhimurium in its free state, complexed with MgATP, or complexed with hydroxycobalamin and MgATP. Biochemistry 40 (2001) 361–374. [DOI] [PMID: 11148030]
3.	Fonseca, M.V. and Escalante-Semerena, J.C. Reduction of Cob(III)alamin to Cob(II)alamin in Salmonella enterica serovar typhimurium LT2. J. Bacteriol. 182 (2000) 4304–4309. [PMID: 10894741]
4.	Fonseca, M.V. and Escalante-Semerena, J.C. An in vitro reducing system for the enzymic conversion of cobalamin to adenosylcobalamin. J. Biol. Chem. 276 (2001) 32101–32108. [DOI] [PMID: 11408479]
5.	Suh, S. and Escalante-Semerena, J.C. Purification and initial characterization of the ATP:corrinoid adenosyltransferase encoded by the cobA gene of Salmonella typhimurium. J. Bacteriol. 177 (1995) 921–925. [DOI] [PMID: 7860601]
6.	Mera, P.E., St Maurice, M., Rayment, I. and Escalante-Semerena, J.C. Residue Phe¹¹² of the human-type corrinoid adenosyltransferase (PduO) enzyme of Lactobacillus reuteri is critical to the formation of the four-coordinate Co(II) corrinoid substrate and to the activity of the enzyme. Biochemistry 48 (2009) 3138–3145. [PMID: 19236001]
7.	Mera, P.E. and Escalante-Semerena, J.C. Dihydroflavin-driven adenosylation of 4-coordinate Co(II) corrinoids: are cobalamin reductases enzymes or electron transfer proteins. J. Biol. Chem. 285 (2010) 2911–2917. [PMID: 19933577]

[EC 2.5.1.17 created 1972, modified 2004, modified 2018]

2.5.1.77

Transferred entry:

7,8-didemethyl-8-hydroxy-5-deazariboflavin synthase. Now EC 2.5.1.147, 5-amino-6-(D-ribitylamino)uracil—L-tyrosine 4-methylphenol transferase and EC 4.3.1.32, 7,8-didemethyl-8-hydroxy-5-deazariboflavin synthase.

[EC 2.5.1.77 created 2010, deleted 2018]

2.5.1.147

Accepted name:

5-amino-6-(D-ribitylamino)uracil—L-tyrosine 4-hydroxyphenyl transferase

Reaction:

5-amino-6-(D-ribitylamino)uracil + L-tyrosine + S-adenosyl-L-methionine = 5-amino-5-(4-hydroxybenzyl)-6-(D-ribitylimino)-5,6-dihydrouracil + 2-iminoacetate + L-methionine + 5′-deoxyadenosine

For diagram of coenzyme F₄₂₀ biosynthesis, click here

Glossary:

5-amino-6-(D-ribitylamino)uracil = 5-amino-6-(1-D-ribitylamino)pyrimidine-2,4(1H,3H)-dione

Other name(s):

cofH (gene name); cbiF (gene name) (ambiguous)

Systematic name:

5-amino-6-(D-ribitylamino)uracil:L-tyrosine, 4-hydroxyphenyl transferase

Comments:

The enzyme is involved in the production of 7,8-didemethyl-8-hydroxy-5-deazariboflavin (FO), the precursor of the redox cofactor coenzyme F₄₂₀, which is found in methanogens and in various actinobacteria. FO is also produced by some cyanobacteria and eukaryotes. The enzyme, which forms a complex with EC 4.3.1.32, 7,8-didemethyl-8-hydroxy-5-deazariboflavin synthase, is a radical SAM enzyme that uses the 5′-deoxyadenosyl radical to initiate the reaction.

Links to other databases:

References:

1.	Decamps, L., Philmus, B., Benjdia, A., White, R., Begley, T.P. and Berteau, O. Biosynthesis of F₀, precursor of the F₄₂₀ cofactor, requires a unique two radical-SAM domain enzyme and tyrosine as substrate. J. Am. Chem. Soc. 134 (2012) 18173–18176. [DOI] [PMID: 23072415]
2.	Philmus, B., Decamps, L., Berteau, O. and Begley, T.P. Biosynthetic versatility and coordinated action of 5′-deoxyadenosyl radicals in deazaflavin biosynthesis. J. Am. Chem. Soc. 137 (2015) 5406–5413. [DOI] [PMID: 25781338]

[EC 2.5.1.147 created 2010 as EC 2.5.1.77, part transferred 2018 to EC 2.5.1.147]

*EC

2.7.2.2

Accepted name:

carbamate kinase

Reaction:

ATP + NH₃ + hydrogencarbonate = ADP + carbamoyl phosphate + H₂O (overall reaction)
(1a) ATP + carbamate = ADP + carbamoyl phosphate
(1b) NH₃ + hydrogencarbonate = carbamate + H₂O (spontaneous)

For diagram of AMP catabolism, click here

Other name(s):

CKase; carbamoyl phosphokinase; carbamyl phosphokinase

Systematic name:

ATP:carbamate phosphotransferase

Comments:

The enzyme catalyses the reversible conversion of carbamoyl phosphate and ADP to ATP and carbamate, which hydrolyses to ammonia and hydrogencarbonate. The physiological role of the enzyme is to generate ATP.

Links to other databases:

BRENDA, EXPASY, Gene, GTD, KEGG, PDB, CAS registry number: 9026-69-1

References:

1.	Jones, M.E., Spector, L. and Lipmann, F. Carbamyl phosphate, the carbamyl donor in enzymatic citrulline synthesis. J. Am. Chem. Soc. 77 (1955) 819–820.
2.	Davis, R.H. Carbamyl phosphate synthesis in Neurospora crassa. I. Preliminary characterization of arginine-specific carbamyl phosphokinase. Biochim. Biophys. Acta 107 (1965) 44–53. [DOI] [PMID: 5857367]
3.	Glasziou, K.T. The metabolism of arginine in Serratia marcescens. II. Carbamyladenosine diphosphate phosphoferase. Aust. J. Biol. Sci. 9 (1956) 253–262.
4.	Bishop, S.H. and Grisolia, S. Crystalline carbamate kinase. Biochim. Biophys. Acta 118 (1966) 211–215. [PMID: 4959296]
5.	Srivenugopal, K.S. and Adiga, P.R. Enzymic conversion of agmatine to putrescine in Lathyrus sativus seedlings. Purification and properties of a multifunctional enzyme (putrescine synthase). J. Biol. Chem. 256 (1981) 9532–9541. [PMID: 6895223]

[EC 2.7.2.2 created 1961, modified 2018]

2.8.5.2

Accepted name:

L-cysteine S-thiosulfotransferase

Reaction:

(1) [SoxY protein]-L-cysteine + thiosulfate + 2 ferricytochrome c = [SoxY protein]-S-sulfosulfanyl-L-cysteine + 2 ferrocytochrome c + 2 H⁺
(2) [SoxY protein]-S-sulfanyl-L-cysteine + thiosulfate + 2 ferricytochrome c = [SoxY protein]-S-(2-sulfodisulfanyl)-L-cysteine + 2 ferrocytochrome c + 2 H⁺

Other name(s):

SoxXA; thiosulfate:[SoxY protein]-L-cysteine thiosulfotransferase

Systematic name:

thiosulfate:[SoxY protein]-L-cysteine thiosulfonotransferase

Comments:

The enzyme is part of the Sox enzyme system, which participates in a bacterial thiosulfate oxidation pathway that produces sulfate. It catalyses two reactions in the pathway - early in the pathway it attaches a thiosulfate molecule to the sulfur atom of an L-cysteine of a SoxY protein; later it transfers a second thiosulfate molecule to a sulfane group that is already attached to the same cysteine residue.

Links to other databases:

References:

1.	Friedrich, C.G., Quentmeier, A., Bardischewsky, F., Rother, D., Kraft, R., Kostka, S. and Prinz, H. Novel genes coding for lithotrophic sulfur oxidation of Paracoccus pantotrophus GB17. J. Bacteriol. 182 (2000) 4677–4687. [PMID: 10940005]
2.	Cheesman, M.R., Little, P.J. and Berks, B.C. Novel heme ligation in a c-type cytochrome involved in thiosulfate oxidation: EPR and MCD of SoxAX from Rhodovulum sulfidophilum. Biochemistry 40 (2001) 10562–10569. [PMID: 11523998]
3.	Rother, D. and Friedrich, C.G. The cytochrome complex SoxXA of Paracoccus pantotrophus is produced in Escherichia coli and functional in the reconstituted sulfur-oxidizing enzyme system. Biochim. Biophys. Acta 1598 (2002) 65–73. [PMID: 12147345]
4.	Bamford, V.A., Bruno, S., Rasmussen, T., Appia-Ayme, C., Cheesman, M.R., Berks, B.C. and Hemmings, A.M. Structural basis for the oxidation of thiosulfate by a sulfur cycle enzyme. EMBO J. 21 (2002) 5599–5610. [PMID: 12411478]
5.	Dambe, T., Quentmeier, A., Rother, D., Friedrich, C. and Scheidig, A.J. Structure of the cytochrome complex SoxXA of Paracoccus pantotrophus, a heme enzyme initiating chemotrophic sulfur oxidation. J. Struct. Biol. 152 (2005) 229–234. [PMID: 16297640]
6.	Hensen, D., Sperling, D., Truper, H.G., Brune, D.C. and Dahl, C. Thiosulphate oxidation in the phototrophic sulphur bacterium Allochromatium vinosum. Mol. Microbiol. 62 (2006) 794–810. [PMID: 16995898]
7.	Grabarczyk, D.B. and Berks, B.C. Intermediates in the Sox sulfur oxidation pathway are bound to a sulfane conjugate of the carrier protein SoxYZ. PLoS One 12:e0173395 (2017). [DOI] [PMID: 28257465]

[EC 2.8.5.2 created 2018]

*EC

3.4.19.9

Accepted name:

folate γ-glutamyl hydrolase

Reaction:

tetrahydropteroyl-(γ-glutamyl)_n + (n-1) H₂O = 5,6,7,8-tetrahydrofolate + (n-1) L-glutamate

For diagram of folate biosynthesis (late stages), click here

Other name(s):

GGH (gene name); conjugase; folate conjugase; lysosomal γ-glutamyl carboxypeptidase; γ-Glu-X carboxypeptidase; pteroyl-poly-γ-glutamate hydrolase; carboxypeptidase G; folic acid conjugase; poly(γ-glutamic acid) endohydrolase; polyglutamate hydrolase; poly(glutamic acid) hydrolase II; pteroylpoly-γ-glutamyl hydrolase; γ-glutamyl hydrolase

Systematic name:

tetrahydropteroyl-poly-γ-glutamyl γ-glutamyl hydrolase

Comments:

The enzyme, which occurs only in animals and plants, can be either endo- and/or exopeptidase. It acts on tetrahydropteroyl polyglutamates and their modified forms, as well as the polyglutamates of the folate breakdown product N-(4-aminobenzoyl)-L-glutamate (pABA-Glu). The initial cleavage may release either monoglutamate or poly-γ-glutamate of two or more residues, depending on the specific enzyme. For example, GGH1 from the plant Arabidopsis thaliana cleaves pentaglutamates, mainly to di- and triglutamates, whereas GGH₂ from the same organism yields mainly monoglutamates. The enzyme is lysosomal (and secreted) in animals and vacuolar in plants. In peptidase family C26.

Links to other databases:

BRENDA, EXPASY, Gene, GTD, KEGG, MEROPS, PDB, CAS registry number: 9074-87-7

References:

1.	McGuire, J.J. and Coward, J.K. Pteroylpolyglutamates: biosynthesis, degradation and function.. In: Blakley, R.L. and Benkovic, S.J. (Ed.), Folates and Pterins, John Wiley and Sons, New York, 1984, pp. 135–191.
2.	Wang, Y., Nimec, Z., Ryan, T.J., Dias, J.A. and Galivan, J. The properties of the secreted γ-glutamyl hydrolases from H35 hepatoma cells. Biochim. Biophys. Acta 1164 (1993) 227–235. [DOI] [PMID: 8343522]
3.	Yao, R., Rhee, M.S. and Galivan, J. Effects of γ-glutamyl hydrolase on folyl and antifolylpolyglutamates in cultured H35 hepatoma cells. Mol. Pharmacol. 48 (1995) 505–511. [PMID: 7565632]
4.	Yao, R., Schneider, E., Ryan, T.J. and Galivan, J. Human γ-glutamyl hydrolase: cloning and characterization of the enzyme expressed in vitro. Proc. Natl. Acad. Sci. USA 93 (1996) 10134–10138. [DOI] [PMID: 8816764]
5.	Yao, R., Nimec, Z., Ryan, T.J. and Galivan, J. Identification, cloning, and sequencing of a cDNA coding for rat γ-glutamyl hydrolase. J. Biol. Chem. 271 (1996) 8525–8528. [DOI] [PMID: 8621474]
6.	Orsomando, G., de la Garza, R.D., Green, B.J., Peng, M., Rea, P.A., Ryan, T.J., Gregory, J.F., 3rd and Hanson, A.D. Plant γ-glutamyl hydrolases and folate polyglutamates: characterization, compartmentation, and co-occurrence in vacuoles. J. Biol. Chem. 280 (2005) 28877–28884. [PMID: 15961386]
7.	Akhtar, T.A., McQuinn, R.P., Naponelli, V., Gregory, J.F., 3rd, Giovannoni, J.J. and Hanson, A.D. Tomato γ-glutamylhydrolases: expression, characterization, and evidence for heterodimer formation. Plant Physiol. 148 (2008) 775–785. [PMID: 18757550]

[EC 3.4.19.9 created 1972 as EC 3.4.12.10, transferred 1978 to EC 3.4.22.12, transferred 1992 to EC 3.4.19.9, modified 1997, modified 2018]

3.6.3.1

Transferred entry:

phospholipid-translocating ATPase. Now EC 7.6.2.1, P-type phospholipid transporter

[EC 3.6.3.1 created 2000 (EC 3.6.3.13 created 2000, incorporated 2001), deleted 2018]

3.6.3.6

Transferred entry:

H⁺-exporting ATPase. Now EC 7.1.2.1, P-type H⁺-exporting transporter

[EC 3.6.3.6 created 1984 as EC 3.6.1.35, transferred 2000 to EC 3.6.3.6, deleted 2018]

3.6.3.7

Transferred entry:

Na⁺-exporting ATPase. Now EC 7.2.2.3, P-type Na⁺ transporter

[EC 3.6.3.7 created 2000, modified 2001, transferred 2018 to EC 7.2.2.3, deleted 2018]

3.6.3.14

Transferred entry:

H⁺-transporting two-sector ATPase. Now EC 7.1.2.2, H⁺-transporting two-sector ATPase

[EC 3.6.3.14 created 1984 as EC 3.6.1.34, transferred 2000 to EC 3.6.3.14, deleted 2018]

3.6.3.15

Transferred entry:

Na⁺-transporting two-sector ATPase. Now EC 7.2.2.1, Na⁺-transporting two-sector ATPase

[EC 3.6.3.15 created 2000, transferred 2018 to EC 7.2.2.1, deleted 2018]

3.6.3.18

Transferred entry:

oligosaccharide-transporting ATPase. Now EC 7.5.2.2, ABC-type oligosaccharide transporter

[EC 3.6.3.18 created 2000, deleted 2018]

3.6.3.19

Transferred entry:

maltose-transporting ATPase. Now EC 7.5.2.1, ABC-type maltose transporter

[EC 3.6.3.19 created 2000, deleted 2018]

3.6.3.21

Transferred entry:

polar-amino-acid-transporting ATPase. Now EC 7.4.2.1, ABC-type polar-amino-acid transporter

[EC 3.6.3.21 created 2000, deleted 2018]

3.6.3.22

Transferred entry:

nonpolar-amino-acid-transporting ATPase. Now EC 7.4.2.2, ABC-type nonpolar-amino-acid transporter

[EC 3.6.3.22 created 2000, deleted 2018]

3.6.3.27

Transferred entry:

phosphate-transporting ATPase. Now EC 7.3.2.1, ABC-type phosphate transporter

[EC 3.6.3.27 created 2000, deleted 2018]

3.6.3.28

Transferred entry:

phosphonate-transporting ATPase. Now EC 7.3.2.2, ABC-type phosphonate transporter

[EC 3.6.3.28 created 2000, deleted 2018]

3.6.3.44

Transferred entry:

xenobiotic-transporting ATPase. Now EC 7.6.2.2, ABC-type xenobiotic transporter

[EC 3.6.3.44 created 2000 (EC 3.6.3.45 incorporated 2006), modified 2006, deleted 2018]

3.6.3.46

Transferred entry:

cadmium-transporting ATPase. Now EC 7.2.2.2, ABC-type Cd²⁺ transporter

[EC 3.6.3.46 created 2000, transferred 2018 to EC 7.2.2.2, deleted 2018]

3.6.4.3

Transferred entry:

microtubule-severing ATPase. Now EC 5.6.1.1, microtubule-severing ATPase

[EC 3.6.4.3 created 2000 as 3.6.4.3, deleted 2018]

3.6.4.11

Deleted entry:

nucleoplasmin ATPase. The activity has been shown not to take place.

[EC 3.6.4.11 created 2000, deleted 2018]

4.1.1.3

Transferred entry:

oxaloacetate decarboxylase. Now recognized to be two enzymes EC 7.2.4.2 [oxaloacetate decarboxylase (Na⁺ extruding)] and EC 4.1.1.112 (oxaloacetate decarboxylase).

[EC 4.1.1.3 created 1961 as EC 4.1.1.3, modified 1986, modified 2000, deleted 2018]

4.1.1.41

Transferred entry:

(S)-methylmalonyl-CoA decarboxylase. Now EC 7.2.4.3, (S)-methylmalonyl-CoA decarboxylase

[EC 4.1.1.41 created 1972, modified 1983, modified 1986, deleted 2018]

*EC

4.1.1.99

Accepted name:

phosphomevalonate decarboxylase

Reaction:

ATP + (R)-5-phosphomevalonate = ADP + phosphate + isopentenyl phosphate + CO₂

For diagram of the archaeal mevalonate pathway, click here

Systematic name:

ATP:(R)-5-phosphomevalonate carboxy-lyase (adding ATP; isopentenyl-phosphate-forming)

Comments:

The enzyme participates in a mevalonate pathway that occurs in halophilic archaea. The activity is also present in eubacteria of the Chloroflexi phylum. cf. EC 4.1.1.33, diphosphomevalonate decarboxylase, and EC 4.1.1.110, bisphosphomevalonate decarboxylase.

Links to other databases:

References:

1.	Dellas, N., Thomas, S.T., Manning, G. and Noel, J.P. Discovery of a metabolic alternative to the classical mevalonate pathway. Elife 2:e00672 (2013). [PMID: 24327557]
2.	Vannice, J.C., Skaff, D.A., Keightley, A., Addo, J.K., Wyckoff, G.J. and Miziorko, H.M. Identification in Haloferax volcanii of phosphomevalonate decarboxylase and isopentenyl phosphate kinase as catalysts of the terminal enzyme reactions in an archaeal alternate mevalonate pathway. J. Bacteriol. 196 (2014) 1055–1063. [DOI] [PMID: 24375100]
3.	Thomas, S.T., Louie, G.V., Lubin, J.W., Lundblad, V. and Noel, J.P. Substrate Specificity and Engineering of Mevalonate 5-Phosphate Decarboxylase. ACS Chem. Biol. 14 (2019) 1767–1779. [PMID: 31268677]

[EC 4.1.1.99 created 2014, modified 2018]

4.1.1.112

Accepted name:

oxaloacetate decarboxylase

Reaction:

oxaloacetate = pyruvate + CO₂

Other name(s):

oxaloacetate β-decarboxylase; oxalacetic acid decarboxylase; oxalate β-decarboxylase; oxaloacetate carboxy-lyase

Systematic name:

oxaloacetate carboxy-lyase (pyruvate-forming)

Comments:

Requires a divalent metal cation. The enzymes from the fish Gadus morhua (Atlantic cod) and the bacterium Micrococcus luteus prefer Mn²⁺, while those from the bacteria Pseudomonas putida and Pseudomonas aeruginosa prefer Mg²⁺. Unlike EC 7.2.4.2 [oxaloacetate decarboxylase (Na⁺ extruding)], there is no evidence of the enzyme’s involvement in Na⁺ transport.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9024-98-0

References:

1.	Schmitt, A., Bottke, I. and Siebert, G. Eigenschaften einer Oxaloacetat-Decarboxylase aus Dorschmuskulatur. Hoppe-Seyler's Z. Physiol. Chem. 347 (1966) 18–34. [PMID: 5972993]
2.	Herbert, D. Oxalacetic carboxylase of Micrococcus lysodeikticus. Methods Enzymol. 1 (1955) 753–757.
3.	Horton, A.A. and Kornberg, H.L. Oxaloacetate 4-carboxy-lyase from Pseudomonas ovalis chester. Biochim. Biophys. Acta 89 (1964) 381–383. [PMID: 14205502]
4.	Sender, P.D., Martin, M.G., Peiru, S. and Magni, C. Characterization of an oxaloacetate decarboxylase that belongs to the malic enzyme family. FEBS Lett. 570 (2004) 217–222. [PMID: 15251467]
5.	Narayanan, B.C., Niu, W., Han, Y., Zou, J., Mariano, P.S., Dunaway-Mariano, D. and Herzberg, O. Structure and function of PA4872 from Pseudomonas aeruginosa, a novel class of oxaloacetate decarboxylase from the PEP mutase/isocitrate lyase superfamily. Biochemistry 47 (2008) 167–182. [PMID: 18081320]

[EC 4.1.1.112 created 1961 as EC 4.1.1.3, modified 1986, modified 2000, part transferred 2018 to EC 4.1.1.112]

4.1.99.24

Accepted name:

L-tyrosine isonitrile synthase

Reaction:

L-tyrosine + D-ribulose 5-phosphate = (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate + hydroxyacetone + formaldehyde + phosphate + H₂O

Glossary:

(2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate = L-tyrosine isonitrile
paerucumarin = 6,7-dihydroxy-3-isocyanochromen-2-one
rhabduscin = N-[(2S,3S,4R,5S,6R)-4,5-dihydroxy-6-{4-[(E)-2-isocyanoethenyl]phenoxy}-2-methyloxan-3-yl]acetamide

Other name(s):

pvcA (gene name)

Systematic name:

L-tyrosine:D-ribulose-5-phosphate lyase (isonitrile-forming)

Comments:

The enzymes from the bacteria Pseudomonas aeruginosa and Xenorhabdus nematophila are involved in the biosynthesis of paerucumarin and rhabduscin, respectively. According to the proposed mechanism, the enzyme forms an imine intermediate composed of linked L-tyrosine and D-ribulose 5-phosphate, followed by loss of the phosphate group and formation of a β-keto imine and keto-enol tautomerization. This is followed by a C-C bond cleavage, the release of hydroxyacetone, and a retro aldol type reaction that releases formaldehyde and forms the final product [3]. cf. EC 4.1.99.25, L-tryptophan isonitrile synthase.

Links to other databases:

References:

1.	Clarke-Pearson, M.F. and Brady, S.F. Paerucumarin, a new metabolite produced by the pvc gene cluster from Pseudomonas aeruginosa. J. Bacteriol. 190 (2008) 6927–6930. [DOI] [PMID: 18689486]
2.	Drake, E.J. and Gulick, A.M. Three-dimensional structures of Pseudomonas aeruginosa PvcA and PvcB, two proteins involved in the synthesis of 2-isocyano-6,7-dihydroxycoumarin. J. Mol. Biol. 384 (2008) 193–205. [DOI] [PMID: 18824174]
3.	Chang, W.C., Sanyal, D., Huang, J.L., Ittiamornkul, K., Zhu, Q. and Liu, X. In vitro stepwise reconstitution of amino acid derived vinyl isocyanide biosynthesis: detection of an elusive intermediate. Org. Lett. 19 (2017) 1208–1211. [DOI] [PMID: 28212039]

[EC 4.1.99.24 created 2018]

4.1.99.25

Accepted name:

L-tryptophan isonitrile synthase

Reaction:

L-tryptophan + D-ribulose 5-phosphate = (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate + hydroxyacetone + formaldehyde + phosphate + H₂O

For diagram of tryptophan isonitrile biosynthesis, click here

Glossary:

(2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate = L-tryptophan isonitrile
hydroxyacetone = 1-hydroxypropan-2-one

Other name(s):

isnA (gene name); ambI1 (gene name); well1 (gene name)

Systematic name:

L-tryptophan:D-ribulose-5-phosphate lyase (isonitrile-forming)

Comments:

The enzymes from cyanobacteria that belong to the Nostocales order participate in the biosynthesis of hapalindole-type alkaloids. According to the proposed mechanism, the enzyme forms an imine intermediate composed of linked L-tryptophan and D-ribulose 5-phosphate, followed by loss of the phosphate group and formation of a β-keto imine and keto-enol tautomerization. This is followed by a C-C bond cleavage, the release of hydroxyacetone, and a retro aldol type reaction that releases formaldehyde and forms the final product [3]. cf. EC 4.1.99.24, L-tyrosine isonitrile synthase.

Links to other databases:

References:

1.	Brady, S.F. and Clardy, J. Cloning and heterologous expression of isocyanide biosynthetic genes from environmental DNA. Angew. Chem. Int. Ed. Engl. 44 (2005) 7063–7065. [PMID: 16206308]
2.	Brady, S.F. and Clardy, J. Systematic investigation of the Escherichia coli metabolome for the biosynthetic origin of an isocyanide carbon atom. Angew. Chem. Int. Ed. Engl. 44 (2005) 7045–7048. [PMID: 16217820]
3.	Hillwig, M.L., Zhu, Q. and Liu, X. Biosynthesis of ambiguine indole alkaloids in cyanobacterium Fischerella ambigua. ACS Chem. Biol. 9 (2014) 372–377. [DOI] [PMID: 24180436]
4.	Chang, W.C., Sanyal, D., Huang, J.L., Ittiamornkul, K., Zhu, Q. and Liu, X. In vitro stepwise reconstitution of amino acid derived vinyl isocyanide biosynthesis: detection of an elusive intermediate. Org. Lett. 19 (2017) 1208–1211. [DOI] [PMID: 28212039]

[EC 4.1.99.25 created 2018]

4.3.1.32

Accepted name:

7,8-didemethyl-8-hydroxy-5-deazariboflavin synthase

Reaction:

5-amino-5-(4-hydroxybenzyl)-6-(D-ribitylimino)-5,6-dihydrouracil + S-adenosyl-L-methionine = 7,8-didemethyl-8-hydroxy-5-deazariboflavin + NH₃ + L-methionine + 5′-deoxyadenosine

For diagram of coenzyme F₄₂₀ biosynthesis, click here

Other name(s):

FO synthase; fbiC (gene name) (ambiguous); cofG (gene name)

Systematic name:

5-amino-5-(4-hydroxybenzyl)-6-(D-ribitylimino)-5,6-dihydrouracil ammonia-lyase (7,8-didemethyl-8-hydroxy-5-deazariboflavin-forming)

Comments:

The enzyme produces the 7,8-didemethyl-8-hydroxy-5-deazariboflavin (FO) precursor of factor 420 (coenzyme F₄₂₀), a metabolite found in methanogens and in various actinobacteria. FO is also produced by some cyanobacteria and eukaryotes. The enzyme, which forms a complex with EC 2.5.1.147, 5-amino-6-(D-ribitylamino)uracil—L-tyrosine 4-hydroxyphenyl transferase, is a radical SAM enzyme that uses the 5′-deoxyadenosyl radical to catalyse the condensation reaction.

Links to other databases:

References:

1.	Decamps, L., Philmus, B., Benjdia, A., White, R., Begley, T.P. and Berteau, O. Biosynthesis of F₀, precursor of the F₄₂₀ cofactor, requires a unique two radical-SAM domain enzyme and tyrosine as substrate. J. Am. Chem. Soc. 134 (2012) 18173–18176. [DOI] [PMID: 23072415]
2.	Philmus, B., Decamps, L., Berteau, O. and Begley, T.P. Biosynthetic versatility and coordinated action of 5′-deoxyadenosyl radicals in deazaflavin biosynthesis. J. Am. Chem. Soc. 137 (2015) 5406–5413. [DOI] [PMID: 25781338]

[EC 4.3.1.32 created 2010 as EC 2.5.1.77, part transferred 2018 to EC 4.3.1.32]

4.3.2.10

Accepted name:

imidazole glycerol-phosphate synthase

Reaction:

5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-β-D-ribosyl)imidazole-4-carboxamide + L-glutamine = 5-amino-1-(5-phospho-β-D-ribosyl)imidazole-4-carboxamide + D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate + L-glutamate (overall reaction)
(1a) L-glutamine + H₂O = L-glutamate + NH₃
(1b) 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-β-D-ribosyl)imidazole-4-carboxamide + NH₃ = 5-amino-1-(5-phospho-β-D-ribosyl)imidazole-4-carboxamide + D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate + H₂O

For diagram of histidine biosynthesis (late stages), click here

Other name(s):

IGP synthase; hisFH (gene names); HIS7 (gene name)

Systematic name:

5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-β-D-ribosyl)imidazole-4-carboxamide D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate-lyase (L-glutamine-hydrolysing; 5-amino-1-(5-phospho-β-D-ribosyl)imidazole-4-carboxamide-forming)

Comments:

The enzyme is involved in histidine biosynthesis, as well as purine nucleotide biosynthesis. The enzymes from archaea and bacteria are heterodimeric. A glutaminase component (cf. EC 3.5.1.2, glutaminase) produces an ammonia molecule that is transferred by a 25 Å tunnel to a cyclase component, which adds it to the imidazole ring, leading to lysis of the molecule and cyclization of one of the products. The glutminase subunit is only active within the dimeric complex. In fungi and plants the two subunits are combined into a single polypeptide.

Links to other databases:

References:

1.	Klem, T.J. and Davisson, V.J. Imidazole glycerol phosphate synthase: the glutamine amidotransferase in histidine biosynthesis. Biochemistry 32 (1993) 5177–5186. [PMID: 8494895]
2.	Fujimori, K. and Ohta, D. An Arabidopsis cDNA encoding a bifunctional glutamine amidotransferase/cyclase suppresses the histidine auxotrophy of a Saccharomyces cerevisiae his7 mutant. FEBS Lett. 428 (1998) 229–234. [PMID: 9654139]
3.	Beismann-Driemeyer, S. and Sterner, R. Imidazole glycerol phosphate synthase from Thermotoga maritima. Quaternary structure, steady-state kinetics, and reaction mechanism of the bienzyme complex. J. Biol. Chem. 276 (2001) 20387–20396. [PMID: 11264293]
4.	Douangamath, A., Walker, M., Beismann-Driemeyer, S., Vega-Fernandez, M.C., Sterner, R. and Wilmanns, M. Structural evidence for ammonia tunneling across the (β α)₈ barrel of the imidazole glycerol phosphate synthase bienzyme complex. Structure 10 (2002) 185–193. [PMID: 11839304]
5.	Chaudhuri, B.N., Lange, S.C., Myers, R.S., Davisson, V.J. and Smith, J.L. Toward understanding the mechanism of the complex cyclization reaction catalyzed by imidazole glycerolphosphate synthase: crystal structures of a ternary complex and the free enzyme. Biochemistry 42 (2003) 7003–7012. [PMID: 12795595]

[EC 4.3.2.10 created 2018]

4.3.99.2

Transferred entry:

carboxybiotin decarboxylase. Now EC 7.2.4.1, carboxybiotin decarboxylase

[EC 4.3.99.2 created 2008, deleted 2018]

4.4.1.6

Transferred entry:

S-alkylcysteine lyase. Now included in EC 4.4.1.13, cysteine-S-conjugate β-lyase

[EC 4.4.1.6 created 1965, deleted 1972, reinstated 1976, deleted 2018]

4.4.1.8

Transferred entry:

cystathionine β-lyase. Now included in EC 4.4.1.13, cysteine-S-conjugate β-lyase

[EC 4.4.1.8 created 1972, deleted 2018]

5.6 Isomerases altering macromolecular conformation

5.6.1 Enzymes altering polypeptide conformation or assembly

5.6.1.1

Accepted name:

microtubule-severing ATPase

Reaction:

n ATP + n H₂O + a microtubule = n ADP + n phosphate + (n+1) α/β tubulin heterodimers

Other name(s):

katanin

Systematic name:

ATP phosphohydrolase (tubulin-dimerizing)

Comments:

A member of the AAA-ATPase family, active in splitting microtubules into tubulin dimers in the centrosome.

Links to other databases:

References:

1.	McNally, F.J. and Vale, R.D. Identification of katanin, an ATPase that severs and disassembles stable microtubules. Cell 75 (1993) 419–429. [DOI] [PMID: 8221885]
2.	Hartman, J.J., Mahr, J., McNally, K., Okawa, K., Iwamatsu, A., Thomas, S., Cheesman, S., Heuser, J., Vale, R.D. and McNally, F.J. Katanin, a microtubule-severing protein, is a novel AAA ATPase that targets to the centrosome using a WD40-containing subunit. Cell 93 (1998) 277–287. [DOI] [PMID: 9568719]

[EC 5.6.1.1 created 2000 as 3.6.4.3, transferred 2018 to EC 5.6.1.1]

*EC

6.2.1.2

Accepted name:

medium-chain acyl-CoA ligase

Reaction:

ATP + a medium-chain fatty acid + CoA = AMP + diphosphate + a medium-chain acyl-CoA

Other name(s):

fadK (gene name); lvaE (gene name); butyryl-CoA synthetase; fatty acid thiokinase (medium chain); acyl-activating enzyme; fatty acid elongase; fatty acid activating enzyme; fatty acyl coenzyme A synthetase; butyrate—CoA ligase; butyryl-coenzyme A synthetase; L-(+)-3-hydroxybutyryl CoA ligase; short-chain acyl-CoA synthetase; medium-chain acyl-CoA synthetase; butanoate:CoA ligase (AMP-forming)

Systematic name:

medium-chain fatty acid:CoA ligase (AMP-forming)

Comments:

Acts on fatty acids from C₄ to C₁₁ and on the corresponding 3-hydroxy and 2,3- or 3,4-unsaturated acids. The enzyme from the bacterium Pseudomonas putida also acts on 4-oxo and 4-hydroxy derivatives.

Links to other databases:

BRENDA, EXPASY, Gene, GTD, KEGG, PDB, CAS registry number: 9080-51-7

References:

1.	Mahler, H.R., Wakil, S.J. and Bock, R.M. Studies on fatty acid oxidation. I. Enzymatic activation of fatty acids. J. Biol. Chem. 204 (1953) 453–468. [PMID: 13084616]
2.	Massaro, E.J. and Lennarz, W.J. The partial purification and characterization of a bacterial fatty acyl coenzyme A synthetase. Biochemistry 4 (1965) 85–90. [PMID: 14285249]
3.	Websterlt, J.R., Gerowin, L.D. and Rakita, L. Purification and characteristics of a butyryl coenzyme A synthetase from bovine heart mitochondria. J. Biol. Chem. 240 (1965) 29–33. [PMID: 14253428]
4.	Morgan-Kiss, R.M. and Cronan, J.E. The Escherichia coli fadK (ydiD) gene encodes an anerobically regulated short chain acyl-CoA synthetase. J. Biol. Chem. 279 (2004) 37324–37333. [PMID: 15213221]
5.	Rand, J.M., Pisithkul, T., Clark, R.L., Thiede, J.M., Mehrer, C.R., Agnew, D.E., Campbell, C.E., Markley, A.L., Price, M.N., Ray, J., Wetmore, K.M., Suh, Y., Arkin, A.P., Deutschbauer, A.M., Amador-Noguez, D. and Pfleger, B.F. A metabolic pathway for catabolizing levulinic acid in bacteria. Nat Microbiol 2 (2017) 1624–1634. [PMID: 28947739]

[EC 6.2.1.2 created 1961, modified 2011, modified 2018]

7 Translocases

7.1 Catalysing the translocation of hydrons

7.1.1 Linked to oxidoreductase reactions

7.1.1.1

Accepted name:

proton-translocating NAD(P)⁺ transhydrogenase

Reaction:

NADPH + NAD⁺ + H⁺_{[side 1]} = NADP⁺ + NADH + H⁺_{[side 2]}

Other name(s):

pntA (gene name); pntB (gene name); NNT (gene name)

Systematic name:

NADPH:NAD⁺ oxidoreductase (H⁺-transporting)

Comments:

The enzyme is a membrane bound proton-translocating pyridine nucleotide transhydrogenase that couples the reversible reduction of NADP by NADH to an inward proton translocation across the membrane. In the bacterium Escherichia coli the enzyme provides a major source of cytosolic NADPH. Detoxification of reactive oxygen species in mitochondria by glutathione peroxidases depends on NADPH produced by this enzyme.

Links to other databases:

References:

1.	Clarke, D.M. and Bragg, P.D. Cloning and expression of the transhydrogenase gene of Escherichia coli. J. Bacteriol. 162 (1985) 367–373. [DOI] [PMID: 3884596]
2.	Clarke, D.M. and Bragg, P.D. Purification and properties of reconstitutively active nicotinamide nucleotide transhydrogenase of Escherichia coli. Eur. J. Biochem. 149 (1985) 517–523. [DOI] [PMID: 3891338]
3.	Glavas, N.A., Hou, C. and Bragg, P.D. Involvement of histidine-91 of the β subunit in proton translocation by the pyridine nucleotide transhydrogenase of Escherichia coli. Biochemistry 34 (1995) 7694–7702. [DOI] [PMID: 7779816]
4.	Sauer, U., Canonaco, F., Heri, S., Perrenoud, A. and Fischer, E. The soluble and membrane-bound transhydrogenases UdhA and PntAB have divergent functions in NADPH metabolism of Escherichia coli. J. Biol. Chem. 279 (2004) 6613–6619. [DOI] [PMID: 14660605]
5.	Bizouarn, T., Fjellstrom, O., Meuller, J., Axelsson, M., Bergkvist, A., Johansson, C., Goran Karlsson, B. and Rydstrom, J. Proton translocating nicotinamide nucleotide transhydrogenase from E. coli. Mechanism of action deduced from its structural and catalytic properties. Biochim. Biophys. Acta 1457 (2000) 211–228. [DOI] [PMID: 10773166]
6.	White, S.A., Peake, S.J., McSweeney, S., Leonard, G., Cotton, N.P. and Jackson, J.B. The high-resolution structure of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase from human heart mitochondria. Structure 8 (2000) 1–12. [DOI] [PMID: 10673423]
7.	Johansson, T., Oswald, C., Pedersen, A., Tornroth, S., Okvist, M., Karlsson, B.G., Rydstrom, J. and Krengel, U. X-ray structure of domain I of the proton-pumping membrane protein transhydrogenase from Escherichia coli. J. Mol. Biol. 352 (2005) 299–312. [DOI] [PMID: 16083909]
8.	Meimaridou, E., Kowalczyk, J., Guasti, L., Hughes, C.R., Wagner, F., Frommolt, P., Nurnberg, P., Mann, N.P., Banerjee, R., Saka, H.N., Chapple, J.P., King, P.J., Clark, A.J. and Metherell, L.A. Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. Nat. Genet. 44 (2012) 740–742. [DOI] [PMID: 22634753]

[EC 7.1.1.1 created 2015 as EC 1.6.1.5, transferred 2018 to EC 7.1.1.1 (EC 1.6.1.2 created 1986, incorporated 2023)]

7.1.1.2

Accepted name:

NADH:ubiquinone reductase (H⁺-translocating)

Reaction:

NADH + H⁺ + an ubiquinone + 4 H⁺_{[side 1]} = NAD⁺ + an ubiquinol + 4 H⁺_{[side 2]}

Other name(s):

ubiquinone reductase (ambiguous); type 1 dehydrogenase; complex 1 dehydrogenase; coenzyme Q reductase (ambiguous); complex I (electron transport chain); complex I (mitochondrial electron transport); complex I (NADH:Q1 oxidoreductase); dihydronicotinamide adenine dinucleotide-coenzyme Q reductase (ambiguous); DPNH-coenzyme Q reductase (ambiguous); DPNH-ubiquinone reductase (ambiguous); mitochondrial electron transport complex 1; mitochondrial electron transport complex I; NADH coenzyme Q₁ reductase; NADH-coenzyme Q oxidoreductase (ambiguous); NADH-coenzyme Q reductase (ambiguous); NADH-CoQ oxidoreductase (ambiguous); NADH-dehydrogenase (ubiquinone) (ambiguous); NADH-CoQ reductase (ambiguous); NADH-ubiquinone reductase (ambiguous); NADH-ubiquinone oxidoreductase (ambiguous); NADH-ubiquinone-1 reductase; reduced nicotinamide adenine dinucleotide-coenzyme Q reductase (ambiguous); NADH:ubiquinone oxidoreductase complex; NADH-Q6 oxidoreductase (ambiguous); electron transfer complex I; NADH₂ dehydrogenase (ubiquinone)

Systematic name:

NADH:ubiquinone oxidoreductase

Comments:

The enzyme is a very large complex that participates in electron transfer chains of mitochondria and aerobic bacteria, transferring two electrons from NADH to a ubiquinone in the membrane's ubiquinone pool while pumping additional protons across the membrane, generating proton motive force. Different reports disagree whether the enzyme pumps 3 or 4 protons. Reversed electron transport through this enzyme can reduce NAD⁺ to NADH.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9028-04-0

References:

1.	Hatefi, Y., Ragan, C.I. and Galante, Y.M. The enzymes and the enzyme complexes of the mitochondrial oxidative phosphorylation system. In: Martonosi, A. (Ed.), The Enzymes of Biological Membranes, 2nd edn, vol. 4, Plenum Press, New York, 1985, pp. 1–70.
2.	Herter, S.M., Kortluke, C.M. and Drews, G. Complex I of Rhodobacter capsulatus and its role in reverted electron transport. Arch. Microbiol. 169 (1998) 98–105. [DOI] [PMID: 9446680]
3.	Hunte, C., Zickermann, V. and Brandt, U. Functional modules and structural basis of conformational coupling in mitochondrial complex I. Science 329 (2010) 448–451. [DOI] [PMID: 20595580]
4.	Efremov, R.G., Baradaran, R. and Sazanov, L.A. The architecture of respiratory complex I. Nature 465 (2010) 441–445. [DOI] [PMID: 20505720]
5.	Wikstrom, M. and Hummer, G. Stoichiometry of proton translocation by respiratory complex I and its mechanistic implications. Proc. Natl. Acad. Sci. USA 109 (2012) 4431–4436. [DOI] [PMID: 22392981]

[EC 7.1.1.2 created 1961 as EC 1.6.5.3, deleted 1965, reinstated 1983, modified 2011, modified 2013, transferred 2018 to EC 7.1.1.2, modified 2023]

7.1 Catalysing the translocation of hydrons

7.1.2 Linked to the hydrolysis of a nucleoside triphosphate

7.1.2.1

Accepted name:

P-type H⁺-exporting transporter

Reaction:

ATP + H₂O + H⁺_{[side 1]} = ADP + phosphate + H⁺_{[side 2]}

Other name(s):

proton-translocating ATPase; yeast plasma membrane H⁺-ATPase; yeast plasma membrane ATPase; ATP phosphohydrolase (ambiguous); proton-exporting ATPase; proton transport ATPase; proton-translocating P-type ATPase; H⁺-transporting ATPase

Systematic name:

ATP phosphohydrolase (P-type, H⁺-exporting)

Comments:

A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. This enzyme occurs in protozoa, fungi and plants, and generates an electrochemical potential gradient of protons across the plasma membrane.

Links to other databases:

References:

1.	Goffeau, A. and Slayman, C. The proton-translocating ATPase of the fungal plasma membrane. Biochim. Biophys. Acta 639 (1981) 197–223. [PMID: 6461354]
2.	Serrano, R., Kielland-Brandt, M.C. and Fink, G.R. Yeast plasma membrane ATPase is essential for growth and has homology with (Na⁺+K⁺)-, K⁺-and Ca²⁺-ATPases. Nature 319 (1986) 689–693. [DOI] [PMID: 3005867]
3.	Serrano, R. and Portillo, F. Catalytic and regulatory sites of yeast plasma membrane H⁺-ATPase studied by directed mutagenesis. Biochim. Biophys. Acta 1018 (1990) 195–199. [DOI] [PMID: 2144186]
4.	Perlin, D.S., San Francisco, M.J., Slayman, C.W. and Rosen, B.P. H⁺/ATP stoichiometry of proton pumps from Neurospora crassa and Escherichia coli. Arch. Biochem. Biophys. 248 (1986) 53–61. [PMID: 2425739]

[EC 7.1.2.1 created 1984 as EC 3.6.1.35, transferred 2000 to EC 3.6.3.6, transferred 2018 to EC 7.1.2.1]

7.1.2.2

Accepted name:

H⁺-transporting two-sector ATPase

Reaction:

ATP + H₂O + 4 H⁺_{[side 1]} = ADP + phosphate + 4 H⁺_{[side 2]}

Glossary:

In Fo, the "o" refers to oligomycin. F₀ is incorrect

Other name(s):

ATP synthase; F₁-ATPase; F_oF₁-ATPase; H⁺-transporting ATPase; mitochondrial ATPase; coupling factors (F_o F₁ and CF1); chloroplast ATPase; bacterial Ca²⁺/Mg²⁺ ATPase

Systematic name:

ATP phosphohydrolase (two-sector, H⁺-transporting)

Comments:

A multisubunit non-phosphorylated ATPase that is involved in the transport of ions. Large enzymes of mitochondria, chloroplasts and bacteria with a membrane sector (Fo, Vo, Ao) and a cytoplasmic-compartment sector (F1, V1, A1). The F-type enzymes of the inner mitochondrial and thylakoid membranes act as ATP synthases. All of the enzymes included here operate in a rotational mode, where the extramembrane sector (containing 3 α- and 3 β-subunits) is connected via the δ-subunit to the membrane sector by several smaller subunits. Within this complex, the γ- and ε-subunits, as well as the 9–12 c subunits rotate by consecutive 120° angles and perform parts of ATP synthesis. This movement is driven by the H⁺ electrochemical potential gradient. The V-type (in vacuoles and clathrin-coated vesicles) and A-type (archaeal) enzymes have a similar structure but, under physiological conditions, they pump H⁺ rather than synthesize ATP.

Links to other databases:

References:

1.	Perlin, D.S., San Francisco, M.J., Slayman, C.W. and Rosen, B.P. H⁺/ATP stoichiometry of proton pumps from Neurospora crassa and Escherichia coli. Arch. Biochem. Biophys. 248 (1986) 53–61. [PMID: 2425739]
2.	Boyer, P.D. The binding change mechanism for ATP synthase - some probabilities and possibilities. Biochim. Biophys. Acta 1140 (1993) 215–250. [DOI] [PMID: 8417777]
3.	Abrahams, J.P., Leslie, A.G.W., Lutter, R. and Walker, J.F. Structure at 2.8 Å resolution of F₁-ATPase from bovine heart mitochondria. Nature 375 (1994) 621–628. [DOI] [PMID: 8065448]
4.	Blair, A., Ngo, L., Park, J., Paulsen, I.T. and Saier, M.H., Jr. Phylogenetic analyses of the homologous transmembrane channel-forming proteins of the F_oF₁-ATPases of bacteria, chloroplasts and mitochondria. Microbiology 142 (1996) 17–32. [DOI] [PMID: 8581162]
5.	Noji, H., Yasuda, R., Yoshida, M. and Kinosita, K., Jr. Direct observation of the rotation of F₁-ATPase. Nature 386 (1997) 299–302. [DOI] [PMID: 9069291]
6.	Turina, P., Samoray, D. and Graber, P. H⁺/ATP ratio of proton transport-coupled ATP synthesis and hydrolysis catalysed by CF₀F₁-liposomes. EMBO J. 22 (2003) 418–426. [PMID: 12554643]

[EC 7.1.2.2 created 1984 as EC 3.6.1.34, transferred 2000 to EC 3.6.3.14, transferred 2018 to EC 7.1.2.2]

7.1 Catalysing the translocation of hydrons

7.1.3 Linked to the hydrolysis of diphosphate

7.1.3.1

Accepted name:

H⁺-exporting diphosphatase

Reaction:

diphosphate + H₂O + H⁺_{[side 1]} = 2 phosphate + H⁺_{[side 2]}

Other name(s):

H⁺-PPase; proton-pumping pyrophosphatase; vacuolar H⁺-pyrophosphatase; hydrogen-translocating pyrophosphatase; proton-pumping dihosphatase

Systematic name:

diphosphate phosphohydrolase (H⁺-transporting)

Comments:

This enzyme, found in plants and fungi, couples the energy from diphosphate hydrolysis to active proton translocation across the tonoplast into the vacuole. The enzyme acts cooperatively with cytosolic soluble diphosphatases to regulate the cytosolic diphosphate level.

Links to other databases:

References:

1.	Rea, P.A. and Poole, R.J. Chromatographic resolution of H⁺-translocating pyrophosphatase from H⁺-translocating ATPase of higher plant tonoplast. Plant Physiol. 81 (1986) 126–129. [PMID: 16664761]
2.	Sarafian, V. and Poole, R.J. Purification of an H⁺-translocating inorganic pyrophosphatase from vacuole membranes of red beet. Plant Physiol. 91 (1989) 34–38. [PMID: 16667022]
3.	Hedrich, R., Kurkdjian, A., Guern, J. and Flugge, U.I. Comparative studies on the electrical properties of the H⁺ translocating ATPase and pyrophosphatase of the vacuolar-lysosomal compartment. EMBO J. 8 (1989) 2835–2841. [PMID: 2479537]
4.	Segami, S., Tomoyama, T., Sakamoto, S., Gunji, S., Fukuda, M., Kinoshita, S., Mitsuda, N., Ferjani, A. and Maeshima, M. Vacuolar H⁺-pyrophosphatase and cytosolic soluble pyrophosphatases cooperatively regulate pyrophosphate levels in Arabidopsis thaliana. Plant Cell 30 (2018) 1040–1061. [PMID: 29691313]

[EC 7.1.3.1 created 2018]

7.2 Catalysing the translocation of inorganic cations

7.2.1 Linked to oxidoreductase reactions

7.2.1.1

Accepted name:

NADH:ubiquinone reductase (Na⁺-transporting)

Reaction:

NADH + H⁺ + ubiquinone + n Na⁺_{[side 1]} = NAD⁺ + ubiquinol + n Na⁺_{[side 2]}

Other name(s):

Na⁺-translocating NADH-quinone reductase; Na⁺-NQR

Systematic name:

NADH:ubiquinone oxidoreductase (Na⁺-translocating)

Comments:

An iron-sulfur flavoprotein, containing two covalently bound molecules of FMN, one noncovalently bound FAD, one riboflavin, and one [2Fe-2S] cluster.

Links to other databases:

References:

1.	Beattie, P., Tan, K., Bourne, R.M., Leach, D., Rich, P.R. and Ward, F.B. Cloning and sequencing of four structural genes for the Na⁺-translocating NADH-ubiquinone oxidoreductase of Vibrio alginolyticus. FEBS Lett. 356 (1994) 333–338. [DOI] [PMID: 7805867]
2.	Nakayama, Y., Hayashi, M. and Unemoto, T. Identification of six subunits constituting Na⁺-translocating NADH-quinone reductase from the marine Vibrio alginolyticus. FEBS Lett. 422 (1998) 240–242. [DOI] [PMID: 9490015]
3.	Bogachev, A.V., Bertsova, Y.V., Barquera, B. and Verkhovsky, M.I. Sodium-dependent steps in the redox reactions of the Na⁺-motive NADH:quinone oxidoreductase from Vibrio harveyi. Biochemistry 40 (2001) 7318–7323. [DOI] [PMID: 11401580]
4.	Barquera, B., Hellwig, P., Zhou, W., Morgan, J.E., Hase, C.C., Gosink, K.K., Nilges, M., Bruesehoff, P.J., Roth, A., Lancaster, C.R. and Gennis, R.B. Purification and characterization of the recombinant Na⁺-translocating NADH:quinone oxidoreductase from Vibrio cholerae. Biochemistry 41 (2002) 3781–3789. [DOI] [PMID: 11888296]
5.	Barquera, B., Nilges, M.J., Morgan, J.E., Ramirez-Silva, L., Zhou, W. and Gennis, R.B. Mutagenesis study of the 2Fe-2S center and the FAD binding site of the Na⁺-translocating NADH:ubiquinone oxidoreductase from Vibrio cholerae. Biochemistry 43 (2004) 12322–12330. [DOI] [PMID: 15379571]

[EC 7.2.1.1 created 2011 as EC 1.6.5.8, transferred 2018 to EC 7.2.1.1]

7.2.1.2

Accepted name:

ferredoxin—NAD⁺ oxidoreductase (Na⁺-transporting)

Reaction:

2 reduced ferredoxin [iron-sulfur] cluster + NAD⁺ + H⁺ + Na⁺_{[side 1]} = 2 oxidized ferredoxin [iron-sulfur] cluster + NADH + Na⁺_{[side 2]}

Other name(s):

Rnf complex (ambiguous); Na⁺-translocating ferredoxin:NAD⁺ oxidoreductase

Systematic name:

ferredoxin:NAD⁺ oxidoreductase (Na⁺-transporting)

Comments:

This iron-sulfur and flavin-containing electron transport complex, isolated from the bacterium Acetobacterium woodii, couples the energy from reduction of NAD⁺ by ferredoxin to pumping sodium ions out of the cell, generating a gradient across the cytoplasmic membrane.

Links to other databases:

References:

1.	Biegel, E., Schmidt, S. and Muller, V. Genetic, immunological and biochemical evidence for a Rnf complex in the acetogen Acetobacterium woodii. Environ. Microbiol. 11 (2009) 1438–1443. [DOI] [PMID: 19222539]
2.	Biegel, E. and Muller, V. Bacterial Na⁺-translocating ferredoxin:NAD⁺ oxidoreductase. Proc. Natl. Acad. Sci. USA 107 (2010) 18138–18142. [DOI] [PMID: 20921383]
3.	Hess, V., Schuchmann, K. and Muller, V. The ferredoxin:NAD⁺ oxidoreductase (Rnf) from the acetogen Acetobacterium woodii requires Na⁺ and is reversibly coupled to the membrane potential. J. Biol. Chem. 288 (2013) 31496–31502. [DOI] [PMID: 24045950]

[EC 7.2.1.2 created 2015 as EC 1.18.1.8, transferred 2018 to EC 7.2.1.2]

7.2 Catalysing the translocation of inorganic cations

7.2.2 Linked to the hydrolysis of a nucleoside triphosphate

7.2.2.1

Accepted name:

Na⁺-transporting two-sector ATPase

Reaction:

ATP + H₂O + n Na⁺_{[side 1]} = ADP + phosphate + n Na⁺_{[side 2]}

Other name(s):

sodium-transporting two-sector ATPase; Na⁺-translocating ATPase; Na⁺-translocating F_oF₁-ATPase; sodium ion specific ATP synthase

Systematic name:

ATP phosphohydrolase (two-sector, Na⁺-transporting)

Comments:

A multisubunit ATPase transporter found in some halophilic or alkalophilic bacteria that functions in maintaining sodium homeostasis. The enzyme is similar to EC 7.1.2.2 (H⁺-transporting two-sector ATPase) but pumps Na⁺ rather than H⁺. By analogy to EC 7.1.2.2, it is likely that the enzyme pumps 4 sodium ions for every ATP molecule that is hydrolysed. cf. EC 7.2.2.3, P-type Na⁺ transporter and EC 7.2.2.4, ABC-type Na⁺ transporter.

Links to other databases:

References:

1.	Solioz, M. and Davies, K. Operon of vacuolar-type Na⁺-ATPase of Enterococcus hirae. J. Biol. Chem. 269 (1994) 9453–9459. [PMID: 8144530]
2.	Takase, K., Kakinuma, S., Yamato, I., Konishi, K., Igarashi, K. and Kanikuma, Y. Sequencing and characterization of the ntp gene cluster for vacuolar-type Na⁺-translocating ATPase of Enterococcus hirae. J. Biol. Chem. 269 (1994) 11037–11044. [PMID: 8157629]
3.	Rahlfs, S. and Müller, V. Sequence of subunit c of the Na⁺-translocating F₁F_o-ATPase of Acetobacterium woodii: proposal for determinants of Na⁺ specificity as revealed by sequence comparisons. FEBS Lett. 404 (1997) 269–271. [DOI] [PMID: 9119076]

[EC 7.2.2.1 created 2000 as EC 3.6.3.15, transferred 2018 to EC 7.2.2.1, modified 2018]

7.2.2.2

Accepted name:

ABC-type Cd²⁺ transporter

Reaction:

ATP + H₂O + Cd²⁺_{[side 1]} = ADP + phosphate + Cd²⁺_{[side 2]}

Other name(s):

cadmium-transporting ATPase (ambiguous); ABC-type cadmium-transporter

Systematic name:

ATP phosphohydrolase (ABC-type, heavy-metal-exporting)

Comments:

An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. Does not undergo phosphorylation during the transport process. A yeast enzyme that exports some heavy metals, especially Cd²⁺, from the cytosol into the vacuole.

Links to other databases:

References:

1.	Li, Z.S., Szczypka, M., Lu, Y.P., Thiele, D.J. and Rea, P.A. The yeast cadmium factor protein (YCF1) is a vacuolar glutathione S-conjugate pump. J. Biol. Chem. 271 (1996) 6509–6517. [DOI] [PMID: 8626454]
2.	Saier, M.H., Jr. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40 (1998) 81–136. [PMID: 9889977]

[EC 7.2.2.2 created 2000 as EC 3.6.3.46, transferred 2018 to EC 7.2.2.2]

7.2.2.3

Accepted name:

P-type Na⁺ transporter

Reaction:

ATP + H₂O + Na⁺_{[side 1]} = ADP + phosphate + Na⁺_{[side 2]}

Other name(s):

Na⁺-exporting ATPase (ambiguous); ENA1 (gene name); ENA2 (gene name); ENA5 (gene name); sodium transport ATPase (ambiguous); sodium-translocating P-type ATPase

Systematic name:

ATP phosphohydrolase (P-type, Na⁺-exporting)

Comments:

A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. This enzyme from yeast is involved in the efflux of Na⁺, with one ion being exported per ATP hydrolysed. Some forms can also export Li⁺ ions. cf. EC 7.2.2.1, Na⁺-transporting two-sector ATPase and EC 7.2.2.4, ABC-type Na⁺ transporter.

Links to other databases:

References:

1.	Wieland, J., Nitsche, A.M., Strayle, J., Steiner, H. and Rudolph, H.K. The PMR2 gene cluster encodes functionally distinct isoforms of a putative Na⁺ pump in the yeast plasma membrane. EMBO J. 14 (1995) 3870–3882. [PMID: 7664728]
2.	Catty, P., de Kerchove d'Exaerde, A. and Goffeau, A. The complete inventory of the yeast Saccharomyces cerevisiae P-type transport ATPases. FEBS Lett. 409 (1997) 325–332. [DOI] [PMID: 9224683]
3.	Benito, B., Quintero, F.J. and Rodriguez-Navarro, A. Overexpression of the sodium ATPase of Saccharomyces cerevisiae: conditions for phosphorylation from ATP and P_i. Biochim. Biophys. Acta 1328 (1997) 214–226. [PMID: 9315618]
4.	Saier, M.H., Jr. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40 (1998) 81–136. [PMID: 9889977]

[EC 7.2.2.3 created 2000 as EC 3.6.3.7, modified 2001, transferred 20018 to EC 7.2.2.3]

7.2.2.4

Accepted name:

ABC-type Na⁺ transporter

Reaction:

ATP + H₂O + Na⁺_{[side 1]} = ADP + phosphate + Na⁺_{[side 2]}

Other name(s):

natAB (gene names)

Systematic name:

ATP phosphohydrolase (ABC-type, Na⁺-exporting)

Comments:

ABC-type (ATP-binding cassette-type) transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. This bacterial enzyme, characterized from Bacillus subtilis, exports Na⁺ ions out of the cell. cf. EC 7.2.2.1, Na⁺-transporting two-sector ATPase and EC 7.2.2.3, P-type Na⁺ transporter.

Links to other databases:

References:

1.	Cheng, J., Guffanti, A.A. and Krulwich, T.A. A two-gene ABC-type transport system that extrudes Na⁺ in Bacillus subtilis is induced by ethanol or protonophore. Mol. Microbiol. 23 (1997) 1107–1120. [DOI] [PMID: 9106203]
2.	Ogura, M., Tsukahara, K., Hayashi, K. and Tanaka, T. The Bacillus subtilis NatK-NatR two-component system regulates expression of the natAB operon encoding an ABC transporter for sodium ion extrusion. Microbiology 153 (2007) 667–675. [PMID: 17322186]

[EC 7.2.2.4 created 2018]

7.2 Catalysing the translocation of inorganic cations

7.2.4 Linked to decarboxylation

*EC

7.2.4.1 – private review period expired (05 July 2024) [Last modified: 2018-09-29 07:05:44]

Accepted name:

carboxybiotin decarboxylase

Reaction:

a carboxybiotinyl-[protein] + n Na⁺_{[side 1]} + H⁺_{[side 2]} = CO₂ + a biotinyl-[protein] + n Na⁺_{[side 2]} (n = 1–2)

For diagram of malonate decarboxylase, click here

Other name(s):

MadB; carboxybiotin protein decarboxylase

Systematic name:

carboxybiotinyl-[protein] carboxy-lyase

Comments:

The integral membrane protein MadB from the anaerobic bacterium Malonomonas rubra is a component of the multienzyme complex EC 7.2.4.4, biotin-dependent malonate decarboxylase. The free energy of the decarboxylation reaction is used to pump Na⁺ out of the cell. The enzyme is a member of the Na⁺-translocating decarboxylase family, other members of which include EC 7.2.4.2 [oxaloacetate decarboxylase (Na⁺ extruding)] and EC 7.2.4.3 [(S)-methylmalonyl-CoA decarboxylase (sodium-transporting)] [2].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, MetaCyc

References:

1.	Berg, M., Hilbi, H. and Dimroth, P. Sequence of a gene cluster from Malonomonas rubra encoding components of the malonate decarboxylase Na⁺ pump and evidence for their function. Eur. J. Biochem. 245 (1997) 103–115. [DOI] [PMID: 9128730]
2.	Dimroth, P. and Hilbi, H. Enzymic and genetic basis for bacterial growth on malonate. Mol. Microbiol. 25 (1997) 3–10. [DOI] [PMID: 11902724]

[EC 7.2.4.1 created 2008 as EC 4.3.99.2, transferred 2018 to EC 7.2.4.1]

7.2.4.2

Accepted name:

oxaloacetate decarboxylase (Na⁺ extruding)

Reaction:

oxaloacetate + 2 Na⁺_{[side 1]} = pyruvate + CO₂ + 2 Na⁺_{[side 2]}

Other name(s):

oxaloacetate β-decarboxylase (ambiguous); oxalacetic acid decarboxylase (ambiguous); oxalate β-decarboxylase (ambiguous); oxaloacetate carboxy-lyase (ambiguous)

Systematic name:

oxaloacetate carboxy-lyase (pyruvate-forming; Na⁺-extruding)

Comments:

The enzyme from the bacterium Klebsiella aerogenes is a biotinyl protein and also decarboxylates glutaconyl-CoA and methylmalonyl-CoA. The process is accompanied by the extrusion of two sodium ions from cells. Some animal enzymes require Mn²⁺. Differs from EC 4.1.1.112 (oxaloacetate decarboxylase) for which there is no evidence for involvement in Na⁺ transport.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9024-98-0

References:

1.	Dimroth, P. Characterization of a membrane-bound biotin-containing enzyme: oxaloacetate decarboxylase from Klebsiella aerogenes. Eur. J. Biochem. 115 (1981) 353–358. [DOI] [PMID: 7016536]
2.	Dimroth, P. The role of biotin and sodium in the decarboxylation of oxaloacetate by the membrane-bound oxaloacetate decarboxylase from Klebsiella aerogenes. Eur. J. Biochem. 121 (1982) 435–441. [DOI] [PMID: 7037395]

[EC 7.2.4.2 created 1961 as EC 4.1.1.3, modified 1986, modified 2000, transferred 2018 to EC 7.2.4.2]

7.2.4.3

Accepted name:

(S)-methylmalonyl-CoA decarboxylase (sodium-transporting)

Reaction:

(S)-methylmalonyl-CoA + Na⁺_{[side 1]} + H⁺_{[side 2]} = propanoyl-CoA + CO₂ + Na⁺_{[side 2]}

Other name(s):

methylmalonyl-coenzyme A decarboxylase (ambiguous); (S)-2-methyl-3-oxopropanoyl-CoA carboxy-lyase (incorrect); (S)-methylmalonyl-CoA carboxy-lyase (ambiguous)

Systematic name:

(S)-methylmalonyl-CoA carboxy-lyase (propanoyl-CoA-forming, sodium-transporting)

Comments:

This bacterial enzyme couples the decarboxylation of (S)-methylmalonyl-CoA to propanoyl-CoA to the vectorial transport of Na⁺ across the cytoplasmic membrane, thereby creating a sodium ion motive force that is used for ATP synthesis. It is a membrane-associated biotin protein and is strictly dependent on sodium ions for activity.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 37289-44-4

References:

1.	Galivan, J.H. and Allen, S.H.G. Methylmalonyl coenzyme A decarboxylase. Its role in succinate decarboxylation by Micrococcus lactilyticus. J. Biol. Chem. 243 (1968) 1253–1261. [PMID: 5646172]
2.	Hilpert, W. and Dimroth, P. Conversion of the chemical energy of methylmalonyl-CoA decarboxylation into a Na⁺ gradient. Nature 296 (1982) 584–585. [PMID: 7070502]
3.	Hoffmann, A., Hilpert, W. and Dimroth, P. The carboxyltransferase activity of the sodium-ion-translocating methylmalonyl-CoA decarboxylase of Veillonella alcalescens. Eur. J. Biochem. 179 (1989) 645–650. [DOI] [PMID: 2920730]
4.	Huder, J.B. and Dimroth, P. Expression of the sodium ion pump methylmalonyl-coenzyme A-decarboxylase from Veillonella parvula and of mutated enzyme specimens in Escherichia coli. J. Bacteriol. 177 (1995) 3623–3630. [PMID: 7601825]
5.	Bott, M., Pfister, K., Burda, P., Kalbermatter, O., Woehlke, G. and Dimroth, P. Methylmalonyl-CoA decarboxylase from Propionigenium modestum^--cloning and sequencing of the structural genes and purification of the enzyme complex. Eur. J. Biochem. 250 (1997) 590–599. [PMID: 9428714]

[EC 7.2.4.3 created 1972 as EC 4.1.1.41, modified 1983, modified 1986, transferred 2018 to EC 7.2.4.3]

7.3 Catalysing the translocation of inorganic anions and their chelates

7.3.2 Linked to the hydrolysis of a nucleoside triphosphate

7.3.2.1

Accepted name:

ABC-type phosphate transporter

Reaction:

ATP + H₂O + phosphate-[phosphate-binding protein]_{[side 1]} = ADP + phosphate + phosphate_{[side 2]} + [phosphate-binding protein]_{[side 1]}

Other name(s):

phosphate ABC transporter; phosphate-transporting ATPase (ambiguous)

Systematic name:

ATP phosphohydrolase (ABC-type, phosphate-importing)

Comments:

An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. A bacterial enzyme that interacts with an extracytoplasmic substrate binding protein and mediates the high affinity uptake of phosphate anions. Unlike P-type ATPases, it does not undergo phosphorylation during the transport process.

Links to other databases:

References:

1.	Webb, D.C., Rosenberg, H. and Cox, G.B. Mutational analysis of the Escherichia coli phosphate-specific transport system, a member of the traffic ATPase (or ABC) family of membrane transporters. A role for proline residues in transmembrane helices. J. Biol. Chem. 267 (1992) 24661–24668. [PMID: 1447208]
2.	Kuan, G., Dassa, E., Saurin, N., Hofnung, M. and Saier, M.H., Jr. Phylogenetic analyses of the ATP-binding constituents of bacterial extracytoplasmic receptor-dependent ABC-type nutrient uptake permeases. Res. Microbiol. 146 (1995) 271–278. [DOI] [PMID: 7569321]
3.	Braibant, M., LeFevre, P., de Wit, L., Ooms, J., Peirs, P., Huygen, K., Wattiez, R. and Content, J. Identification of a second Mycobacterium tuberculosis gene cluster encoding proteins of an ABC phosphate transporter. FEBS Lett. 394 (1996) 206–212. [DOI] [PMID: 8843165]
4.	Saier, M.H., Jr. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40 (1998) 81–136. [PMID: 9889977]
5.	Griffiths, J.K. and Sansom, C.E. The Transporter Factsbook, Academic Press, San Diego, 1998.

[EC 7.3.2.1 created 2000 as EC 3.6.3.27, transferred 2018 to EC 7.3.2.1]

7.3.2.2

Accepted name:

ABC-type phosphonate transporter

Reaction:

ATP + H₂O + phosphonate-[phosphonate-binding protein]_{[side 1]} = ADP + phosphate + phosphonate_{[side 2]} + [phosphonate-binding protein]_{[side 1]}

Other name(s):

phosphonate-transporting ATPase (ambiguous)

Systematic name:

ATP phosphohydrolase (ABC-type, phosphonate-importing)

Comments:

An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. The enzyme, found in bacteria, interacts with an extracytoplasmic substrate binding protein and mediates the import of phosphonate and organophosphate anions.

Links to other databases:

References:

1.	Wanner, B.L. and Metcalf, W.W. Molecular genetic studies of a 10.9-kb operon in Escherichia coli for phosphonate uptake and biodegradation. FEMS Microbiol. Lett. 79 (1992) 133–139. [PMID: 1335942]
2.	Kuan, G., Dassa, E., Saurin, N., Hofnung, M. and Saier, M.H., Jr. Phylogenetic analyses of the ATP-binding constituents of bacterial extracytoplasmic receptor-dependent ABC-type nutrient uptake permeases. Res. Microbiol. 146 (1995) 271–278. [DOI] [PMID: 7569321]
3.	Saier, M.H., Jr. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40 (1998) 81–136. [PMID: 9889977]
4.	Griffiths, J.K. and Sansom, C.E. The Transporter Factsbook, Academic Press, San Diego, 1998.

[EC 7.3.2.2 created 2000 as EC 3.6.3.28, transferred 2018 to EC 7.3.2.2]

7.4 Catalysing the translocation of amino acids and peptides

7.4.2 Linked to the hydrolysis of a nucleoside triphosphate

7.4.2.1

Accepted name:

ABC-type polar-amino-acid transporter

Reaction:

ATP + H₂O + polar amino acid-[polar amino acid-binding protein]_{[side 1]} = ADP + phosphate + polar amino acid_{[side 2]} + [polar amino acid-binding protein]_{[side 1]}

Glossary:

nopaline = N-{(1R)-1-carboxy-4-[(diaminomethylene)amino]butyl}-L-glutamate

Other name(s):

histidine permease; polar-amino-acid-transporting ATPase

Systematic name:

ATP phosphohydrolase (ABC-type, polar-amino-acid-importing)

Comments:

Links to other databases:

References:

1.	Kuan, G., Dassa, E., Saurin, N., Hofnung, M. and Saier, M.H., Jr. Phylogenetic analyses of the ATP-binding constituents of bacterial extracytoplasmic receptor-dependent ABC-type nutrient uptake permeases. Res. Microbiol. 146 (1995) 271–278. [DOI] [PMID: 7569321]
2.	Nikaido, K., Liu, P.Q. and Ferro-Luzzi Ames, G. Purification and characterization of HisP, the ATP-binding subunit of a traffic ATPase (ABC transporter), the histidine permease of Salmonella typhimurium. Solubilization, dimerization , and ATPase activity. J. Biol. Chem. 272 (1997) 27745–27752. [DOI] [PMID: 9346917]
3.	Walshaw, D.L., Lowthorpe, S., East, A. and Poole, P.S. Distribution of a sub-class of bacterial ABC polar amino acid transporter and identification of an N-terminal region involved in solute specificity. FEBS Lett. 414 (1997) 397–401. [DOI] [PMID: 9315727]
4.	Saier, M.H., Jr. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40 (1998) 81–136. [PMID: 9889977]

[EC 7.4.2.1 created 2000 as EC 3.6.3.21, transferred 2018 to EC 7.4.2.1]

7.4.2.2

Accepted name:

ABC-type nonpolar-amino-acid transporter

Reaction:

ATP + H₂O + nonpolar amino acid-[nonpolar amino acid-binding protein]_{[side 1]} = ADP + phosphate + nonpolar amino acid_{[side 2]} + [nonpolar amino acid-binding protein]_{[side 1]}

Other name(s):

nonpolar-amino-acid-transporting ATPase

Systematic name:

ATP phosphohydrolase (ABC-type, nonpolar-amino-acid-importing)

Comments:

An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. The enzyme, found in bacteria, interacts with an extracytoplasmic substrate binding protein. This entry comprises enzymes that import Leu, Ile and Val.

Links to other databases:

References:

1.	Kuan, G., Dassa, E., Saurin, N., Hofnung, M. and Saier, M.H., Jr. Phylogenetic analyses of the ATP-binding constituents of bacterial extracytoplasmic receptor-dependent ABC-type nutrient uptake permeases. Res. Microbiol. 146 (1995) 271–278. [DOI] [PMID: 7569321]
2.	Saier, M.H., Jr. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40 (1998) 81–136. [PMID: 9889977]
3.	Griffiths, J.K. and Sansom, C.E. The Transporter Factsbook, Academic Press, San Diego, 1998.

[EC 7.4.2.2 created 2000 as EC 3.6.3.22, transferred 2018 to EC 7.4.2.2]

7.5 Catalysing the translocation of carbohydrates and their derivatives

7.5.2 Linked to the hydrolysis of a nucleoside triphosphate

7.5.2.1

Accepted name:

ABC-type maltose transporter

Reaction:

ATP + H₂O + maltose-[maltose-binding protein]_{[side 1]} = ADP + phosphate + maltose_{[side 2]} + [maltose-binding protein]_{[side 1]}

Other name(s):

maltose ABC transporter; maltose-transporting ATPase

Systematic name:

ATP phosphohydrolase (ABC-type, maltose-importing)

Comments:

Links to other databases:

References:

1.	Higgins, C.F. ABC transporters: from microorganisms to man. Annu. Rev. Cell Biol. 8 (1992) 67–113. [DOI] [PMID: 1282354]
2.	Dassa, E. and Muir, S. Membrane topology of MalG, an inner membrane protein from the maltose transport system of Escherichia coli. Mol. Microbiol. 7 (1993) 29–38. [DOI] [PMID: 8437518]
3.	Kuan, G., Dassa, E., Saurin, N., Hofnung, M. and Saier, M.H., Jr. Phylogenetic analyses of the ATP-binding constituents of bacterial extracytoplasmic receptor-dependent ABC-type nutrient uptake permeases. Res. Microbiol. 146 (1995) 271–278. [DOI] [PMID: 7569321]
4.	Saier, M.H., Jr. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40 (1998) 81–136. [PMID: 9889977]
5.	Griffiths, J.K. and Sansom, C.E. The Transporter Factsbook, Academic Press, San Diego, 1998.

[EC 7.5.2.1 created 2000 as EC 3.6.3.19, transferred 2018 to EC 7.5.2.1]

7.5.2.2

Accepted name:

ABC-type oligosaccharide transporter

Reaction:

ATP + H₂O + oligosaccharide-[oligosaccharide-binding protein]_{[side 1]} = ADP + phosphate + oligosaccharide_{[side 2]} + [oligosaccharide-binding protein]_{[side 1]}

Other name(s):

oligosaccharide-transporting ATPase

Systematic name:

ATP phosphohydrolase (ABC-type, oligosaccharide-importing)

Comments:

Links to other databases:

References:

1.	Higgins, C.F. ABC transporters: from microorganisms to man. Annu. Rev. Cell Biol. 8 (1992) 67–113. [DOI] [PMID: 1282354]
2.	Williams, S.G., Greenwood, J.A. and Jones, C.W. Molecular analysis of the lac operon encoding the binding-protein-dependent lactose transport system and β-galactosidase in Agrobacterium radiobacter. Mol. Microbiol. 6 (1992) 1755–1768. [DOI] [PMID: 1630315]
3.	Tam, R. and Saier, M.H., Jr. Structural, functional, and evolutionary relationships among extracellular solute-binding receptors of bacteria. Microbiol. Rev. 57 (1993) 320–346. [PMID: 8336670]
4.	Kuan, G., Dassa, E., Saurin, N., Hofnung, M. and Saier, M.H., Jr. Phylogenetic analyses of the ATP-binding constituents of bacterial extracytoplasmic receptor-dependent ABC-type nutrient uptake permeases. Res. Microbiol. 146 (1995) 271–278. [DOI] [PMID: 7569321]
5.	Saier, M.H., Jr. Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya. Adv. Microb. Physiol. 40 (1998) 81–136. [PMID: 9889977]

[EC 7.5.2.2 created 2000 as EC 3.6.3.18, transferred 2018 to EC 7.5.2.2]

7.6 Catalysing the translocation of other compounds

7.6.2 Linked to the hydrolysis of a nucleoside triphosphate

7.6.2.1

Accepted name:

P-type phospholipid transporter

Reaction:

ATP + H₂O + phospholipid_{[side 1]} = ADP + phosphate + phospholipid_{[side 2]}

Other name(s):

Mg²⁺-ATPase (ambiguous); flippase (ambiguous); aminophospholipid-transporting ATPase (ambiguous); phospholipid-translocating ATPase (ambiguous); phospholipid-transporting ATPase (ambiguous)

Systematic name:

ATP phosphohydrolase (P-type, phospholipid-flipping)

Comments:

A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. Different forms of the enzyme move phospholipids such as phosphatidylcholine, lyso-phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, phosphatidyglycerol, sphingomyelin and glucosylceramide from one membrane face to the other (‘flippase’).

Links to other databases:

References:

1.	Morris, M.B., Auland, M.E., Xu, Y.H. and Roufogalis, B.D. Characterization of the Mg²⁺-ATPase activity of the human erythrocyte membrane. Biochem. Mol. Biol. Int. 31 (1993) 823–832. [PMID: 8136700]
2.	Vermeulen, W.P., Briede, J.J. and Rolofsen, B. Manipulation of the phosphatidylethanolamine pool in the human red cell membrane affects its Mg²⁺-ATPase activity. Mol. Membr. Biol. 13 (1996) 95–102. [PMID: 8839453]
3.	Suzuki, H., Kamakura, M., Morii, M. and Takeguchi, N. The phospholipid flippase activity of gastric vesicles. J. Biol. Chem. 272 (1997) 10429–10434. [DOI] [PMID: 9099684]
4.	Auland, M.E., Roufogalis, B.D., Devaux, P.F. and Zachowski, A. Reconstitution of ATP-dependent aminophospholipid translocation in proteoliposomes. Proc. Natl. Acad. Sci. USA 91 (1994) 10938–10942. [DOI] [PMID: 7971987]
5.	Alder-Baerens, N., Lisman, Q., Luong, L., Pomorski, T. and Holthuis, J.C. Loss of P4 ATPases Drs2p and Dnf3p disrupts aminophospholipid transport and asymmetry in yeast post-Golgi secretory vesicles. Mol. Biol. Cell 17 (2006) 1632–1642. [DOI] [PMID: 16452632]
6.	Lopez-Marques, R.L., Poulsen, L.R., Hanisch, S., Meffert, K., Buch-Pedersen, M.J., Jakobsen, M.K., Pomorski, T.G. and Palmgren, M.G. Intracellular targeting signals and lipid specificity determinants of the ALA/ALIS P4-ATPase complex reside in the catalytic ALA α-subunit. Mol. Biol. Cell 21 (2010) 791–801. [DOI] [PMID: 20053675]
7.	Jensen, M.S., Costa, S.R., Duelli, A.S., Andersen, P.A., Poulsen, L.R., Stanchev, L.D., Gourdon, P., Palmgren, M., Günther Pomorski, T. and Lopez-Marques, R.L. Phospholipid flipping involves a central cavity in P4 ATPases. Sci. Rep. 7:17621 (2017). [PMID: 29247234]

[EC 7.6.2.1 created 2000 as EC 3.6.3.1 (EC 3.6.3.13 created 2000, incorporated 2001), transferred 2018 to EC 7.6.2.1]

7.6.2.2

Accepted name:

ABC-type xenobiotic transporter

Reaction:

ATP + H₂O + xenobiotic_{[side 1]} = ADP + phosphate + xenobiotic_{[side 2]}

Other name(s):

xenobiotic-transporting ATPase; multidrug-resistance protein; MDR protein; P-glycoprotein; pleiotropic-drug-resistance protein; PDR protein; steroid-transporting ATPase; ATP phosphohydrolase (steroid-exporting)

Systematic name:

ATP phosphohydrolase (ABC-type, xenobiotic-exporting)

Comments:

An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. Does not undergo phosphorylation during the transport process. The enzymes from Gram-positive bacteria and eukaryotic cells export a number of drugs with unusual specificity, covering various groups of unrelated substances while ignoring some that are closely related structurally. Several distinct enzymes may be present in a single eukaryotic cell. Many of them also transport glutathione—drug conjugates (see EC 7.6.2.3, ABC-type glutathione-S-conjugate transporter) while others also show some ’flippase’ activity (cf. EC 7.6.2.1, P-type phospholipid transporter).

Links to other databases:

References:

1.	Bellamy, W.T. P-glycoproteins and multidrug resistance. Annu. Rev. Pharmacol. Toxicol. 36 (1996) 161–183. [DOI] [PMID: 8725386]
2.	Frijters, C.M., Ottenhoff, R., Van Wijland, M.J., Van Nieuwkerk, C., Groen, A.K. and Oude-Elferink, R.P. Influence of bile salts on hepatic mdr2 P-glycoprotein expression. Adv. Enzyme Regul. 36 (1996) 351–363. [DOI] [PMID: 8869755]
3.	Keppler, D., König, J. and Buchler, M. The canalicular multidrug resistance protein, cMRP/MRP2, a novel conjugate export pump expressed in the apical membrane of hepatocytes. Adv. Enzyme Regul. 37 (1997) 321–333. [DOI] [PMID: 9381978]
4.	Loe, D.W., Deeley, R.G. and Cole, S.P. Characterization of vincristine transport by the M_r 190,000 multidrug resistance protein (MRP): evidence for cotransport with reduced glutathione. Cancer Res. 58 (1998) 5130–5136. [PMID: 9823323]
5.	van Veen, H.W. and Konings, W.N. The ABC family of multidrug transporters in microorganisms. Biochim. Biophys. Acta 1365 (1998) 31–36. [DOI] [PMID: 9693718]
6.	Griffiths, J.K. and Sansom, C.E. The Transporter Factsbook, Academic Press, San Diego, 1998.
7.	Prasad, R., De Wergifosse, P., Goffeau, A. and Balzi, E. Molecular cloning and characterization of a novel gene of Candida albicans, CDR1, conferring multiple resistance to drugs and antifungals. Curr. Genet. 27 (1995) 320–329. [PMID: 7614555]
8.	Nagao, K., Taguchi, Y., Arioka, M., Kadokura, H., Takatsuki, A., Yoda, K. and Yamasaki, M. bfr1⁺, a novel gene of Schizosaccharomyces pombe which confers brefeldin A resistance, is structurally related to the ATP-binding cassette superfamily. J. Bacteriol. 177 (1995) 1536–1543. [DOI] [PMID: 7883711]
9.	Mahé, Y., Lemoine, Y. and Kuchler, K. The ATP-binding cassette transporters Pdr5 and Snq2 of Saccharomyces cerevisiae can mediate transport of steroids in vivo. J. Biol. Chem. 271 (1996) 25167–25172. [DOI] [PMID: 8810273]

[EC 7.6.2.2 created 2000 as EC 3.6.3.44 (EC 3.6.3.45 incorporated 2006), modified 2006, transferred 2018 to EC 7.6.2.2]

7.6.2.3

Accepted name:

ABC-type glutathione-S-conjugate transporter

Reaction:

ATP + H₂O + glutathione-S-conjugate_{[side 1]} = ADP + phosphate + glutathione-S-conjugate_{[side 2]}

Other name(s):

multidrug resistance-associated protein 1; glutathione-S-conjugate-translocating ATPase; MRP; MRP1; ABCC1 (gene name); YBT1 (gene name); YCF1 (gene name)

Systematic name:

ATP phosphohydrolase (ABC-type, glutathione-S-conjugate-exporting)

Comments:

A eukaryotic ATP-binding cassette (ABC) type transporter that mediates the transport of glutathione-S-conjugates. The mammalian enzyme, which also transports some glucuronides, exports the substrates out of the cell, while plant and fungal transporters export them into the vacuole. Over-expression confers resistance to anticancer drugs by their efficient exportation in glutathione-S-conjugate form.

Links to other databases: