Proposed Changes to the Enzyme List

References:

1.	Lee, S.B., Cho, S.J., Kim, J.A., Lee, S.Y., Kim, S.M. and Lim, H.S. Metabolic pathway of 3,6-anhydro-L-galactose in agar-degrading microorganisms. Biotechnol. Bioprocess Eng. 19 (2014) 866–878.

[EC 1.1.1.389 created 2015]

1.1.1.390

Accepted name:

sulfoquinovose 1-dehydrogenase

Reaction:

sulfoquinovose + NAD⁺ = 6-deoxy-6-sulfo-D-glucono-1,5-lactone + NADH + H⁺

For diagram of sulphoglycolysis of sulfoquinovose, click here

Glossary:

sulfoquinovose = 6-deoxy-6-sulfo-D-glucopyranose

Systematic name:

6-deoxy-6-sulfo-D-glucopyranose:NAD⁺ 1-oxidoreductase

Comments:

The enzyme, characterized from the bacterium Pseudomonas putida SQ1, participates in a sulfoquinovose degradation pathway. Activity with NADP⁺ is only 4% of that with NAD⁺.

Links to other databases:

References:

1.	Felux, A.K., Spiteller, D., Klebensberger, J. and Schleheck, D. Entner-Doudoroff pathway for sulfoquinovose degradation in Pseudomonas putida SQ1. Proc. Natl. Acad. Sci. USA 112 (2015) E4298–E4305. [DOI] [PMID: 26195800]

[EC 1.1.1.390 created 2015]

*EC

1.2.1.64

Accepted name:

4-hydroxybenzaldehyde dehydrogenase (NAD⁺)

Reaction:

4-hydroxybenzaldehyde + NAD⁺ + H₂O = 4-hydroxybenzoate + NADH + 2 H⁺

Other name(s):

p-hydroxybenzaldehyde dehydrogenase (ambiguous); 4-hydroxybenzaldehyde dehydrogenase (ambiguous)

Systematic name:

4-hydroxybenzaldehyde:NAD⁺ oxidoreductase

Comments:

The bacterial enzyme (characterized from an unidentified denitrifying bacterium) is involved in an anaerobic toluene degradation pathway. The plant enzyme is involved in formation of 4-hydroxybenzoate, a cell wall-bound phenolic acid that plays a major role in plant defense against pathogens. cf. EC 1.2.1.96, 4-hydroxybenzaldehyde dehydrogenase (NADP⁺).

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, CAS registry number: 61229-72-9

References:

1.	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]
2.	Sircar, D. and Mitra, A. Evidence for p-hydroxybenzoate formation involving enzymatic phenylpropanoid side-chain cleavage in hairy roots of Daucus carota. J. Plant Physiol. 165 (2008) 407–414. [DOI] [PMID: 17658659]

[EC 1.2.1.64 created 2000, modified 2015]

1.2.1.96

Accepted name:

4-hydroxybenzaldehyde dehydrogenase (NADP⁺)

Reaction:

4-hydroxybenzaldehyde + NADP⁺ + H₂O = 4-hydroxybenzoate + NADPH + 2 H⁺

Other name(s):

p-hydroxybenzaldehyde dehydrogenase (ambiguous); pchA (gene name)

Systematic name:

4-hydroxybenzaldehyde:NADP⁺ oxidoreductase

Comments:

Involved in the aerobic pathway for degradation of toluene, 4-methylphenol, and 2,4-xylenol by several Pseudomonas strains. The enzyme is also active with 4-hydroxy-3-methylbenzaldehyde. cf. EC 1.2.1.64, 4-hydroxybenzaldehyde dehydrogenase (NAD⁺).

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, CAS registry number: 61229-72-9

References:

1.	Whited, G.M. and Gibson, D.T. Separation and partial characterization of the enzymes of the toluene-4-monooxygenase catabolic pathway in Pseudomonas mendocina KR1. J. Bacteriol. 173 (1991) 3017–3020. [DOI] [PMID: 2019564]
2.	Chen, Y.F., Chao, H. and Zhou, N.Y. The catabolism of 2,4-xylenol and p-cresol share the enzymes for the oxidation of para-methyl group in Pseudomonas putida NCIMB 9866. Appl. Microbiol. Biotechnol. 98 (2014) 1349–1356. [DOI] [PMID: 23736872]

[EC 1.2.1.96 created 2015]

1.2.1.97

Accepted name:

3-sulfolactaldehyde dehydrogenase

Reaction:

(2S)-3-sulfolactaldehyde + NAD(P)⁺ + H₂O = (2S)-3-sulfolactate + NAD(P)H + H⁺

For diagram of sulphoglycolysis of sulfoquinovose, click here

Glossary:

(2S)-3-sulfolactaldehyde = (2S)-2-hydroxy-3-oxopropane-1-sulfonate

Other name(s):

SLA dehydrogenase

Systematic name:

(2S)-3-sulfolactaldehyde:NAD(P)⁺ oxidoreductase

Comments:

The enzyme, characterized from the bacterium Pseudomonas putida SQ1, participates in a sulfoquinovose degradation pathway. Also acts on succinate semialdehyde.

Links to other databases:

References:

1.	Felux, A.K., Spiteller, D., Klebensberger, J. and Schleheck, D. Entner-Doudoroff pathway for sulfoquinovose degradation in Pseudomonas putida SQ1. Proc. Natl. Acad. Sci. USA 112 (2015) E4298–E4305. [DOI] [PMID: 26195800]

[EC 1.2.1.97 created 2015]

1.3.1.108

Accepted name:

caffeoyl-CoA reductase

Reaction:

3-(3,4-dihydroxyphenyl)propanoyl-CoA + 2 NAD⁺ + 2 reduced ferredoxin [iron-sulfur] cluster = (2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl-CoA + 2 NADH + 2 oxidized ferredoxin [iron-sulfur] cluster

Glossary:

(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl-CoA = (2E)-3-(3,4-dihydroxyphenyl)acryloyl-CoA = trans-caffeoyl-CoA
3-(3,4-dihydroxyphenyl)propanoyl-CoA = hydrocaffeoyl-CoA

Other name(s):

electron-bifurcating caffeoyl-CoA reductase; caffeoyl-CoA reductase-Etf complex; hydrocaffeoyl-CoA:NAD⁺,ferredoxin oxidoreductase

Systematic name:

3-(3,4-dihydroxyphenyl)propanoyl-CoA:NAD⁺,ferredoxin oxidoreductase

Comments:

The enzyme, characterized from the bacterium Acetobacterium woodii, contains two [4Fe-4S] clusters and FAD. The enzyme couples the endergonic ferredoxin reduction with NADH as reductant to the exergonic reduction of caffeoyl-CoA with the same reductant. It uses the mechanism of electron bifurcation to overcome the steep energy barrier in ferredoxin reduction. It also reduces 4-coumaroyl-CoA and feruloyl-CoA.

Links to other databases:

References:

1.	Bertsch, J., Parthasarathy, A., Buckel, W. and Muller, V. An electron-bifurcating caffeyl-CoA reductase. J. Biol. Chem. 288 (2013) 11304–11311. [DOI] [PMID: 23479729]

[EC 1.3.1.108 created 2015]

1.3.1.109

Accepted name:

butanoyl-CoA dehydrogenase complex (NAD⁺, ferredoxin)

Reaction:

butanoyl-CoA + 2 NAD⁺ + 2 reduced ferredoxin [iron-sulfur] cluster = (E)-but-2-enoyl-CoA + 2 NADH + 2 oxidized ferredoxin [iron-sulfur] cluster

Glossary:

(E)-but-2-enoyl-CoA = crotonyl-CoA

Other name(s):

bifurcating butyryl-CoA dehydrogenase; butyryl-CoA dehydrogenase/Etf complex; Etf-Bcd complex; bifurcating butanoyl-CoA dehydrogenase; butanoyl-CoA dehydrogenase/Etf complex; butanoyl-CoA dehydrogenase (NAD⁺, ferredoxin)

Systematic name:

butanoyl-CoA:NAD⁺, ferredoxin oxidoreductase

Comments:

The enzyme is a complex of a flavin-containing dehydrogenase component (Bcd) and an electron-transfer flavoprotein dimer (EtfAB). The enzyme complex, isolated from the bacteria Acidaminococcus fermentans and butanoate-producing Clostridia species, couples the exergonic reduction of (E)-but-2-enoyl-CoA to butanoyl-CoA by NADH to the endergonic reduction of ferredoxin by NADH, using electron bifurcation to overcome the steep energy barrier in ferredoxin reduction.

Links to other databases:

References:

1.	Li, F., Hinderberger, J., Seedorf, H., Zhang, J., Buckel, W. and Thauer, R.K. Coupled ferredoxin and crotonyl coenzyme A (CoA) reduction with NADH catalyzed by the butyryl-CoA dehydrogenase/Etf complex from Clostridium kluyveri. J. Bacteriol. 190 (2008) 843–850. [DOI] [PMID: 17993531]
2.	Aboulnaga el,-H., Pinkenburg, O., Schiffels, J., El-Refai, A., Buckel, W. and Selmer, T. Effect of an oxygen-tolerant bifurcating butyryl coenzyme A dehydrogenase/electron-transferring flavoprotein complex from Clostridium difficile on butyrate production in Escherichia coli. J. Bacteriol. 195 (2013) 3704–3713. [DOI] [PMID: 23772070]
3.	Chowdhury, N.P., Mowafy, A.M., Demmer, J.K., Upadhyay, V., Koelzer, S., Jayamani, E., Kahnt, J., Hornung, M., Demmer, U., Ermler, U. and Buckel, W. Studies on the mechanism of electron bifurcation catalyzed by electron transferring flavoprotein (Etf) and butyryl-CoA dehydrogenase (Bcd) of Acidaminococcus fermentans. J. Biol. Chem. 289 (2014) 5145–5157. [DOI] [PMID: 24379410]
4.	Chowdhury, N.P., Kahnt, J. and Buckel, W. Reduction of ferredoxin or oxygen by flavin-based electron bifurcation in Megasphaera elsdenii. FEBS J. 282 (2015) 3149–3160. [DOI] [PMID: 25903584]

[EC 1.3.1.109 created 2015, modified 2021]

1.3.1.110

Transferred entry:

lactate dehydrogenase (NAD⁺, ferredoxin). Now EC 1.1.1.436, lactate dehydrogenase (NAD⁺,ferredoxin)

[EC 1.3.1.110 created 2015, deleted 2022]

*EC

1.5.3.5

Accepted name:

(S)-6-hydroxynicotine oxidase

Reaction:

(S)-6-hydroxynicotine + H₂O + O₂ = 1-(6-hydroxypyridin-3-yl)-4-(methylamino)butan-1-one + H₂O₂ (overall reaction)
(1a) (S)-6-hydroxynicotine + O₂ = 5-(N-methyl-4,5-dihydro-1H-pyrrol-2-yl)pyridin-2-ol + H₂O₂
(1b) 5-(N-methyl-4,5-dihydro-1H-pyrrol-2-yl)pyridin-2-ol + H₂O = 1-(6-hydroxypyridin-3-yl)-4-(methylamino)butan-1-one (spontaneous)

For diagram of nicotine catabolism by arthrobacter, click here

Glossary:

(S)-6-hydroxynicotine = 5-[(2S)-1-methylpyrrolidin-2-yl]pyridin-2-ol
1-(6-hydroxypyridin-3-yl)-4-(methylamino)butan-1-one = 6-hydroxypseudooxynicotine
5-(N-methyl-4,5-dihydro-1H-pyrrol-2-yl)pyridin-2-ol = 6-hydroxy-N-methylmyosmine

Other name(s):

L-6-hydroxynicotine oxidase; 6-hydroxy-L-nicotine oxidase; 6-hydroxy-L-nicotine:oxygen oxidoreductase; nctB (gene name)

Systematic name:

(S)-6-hydroxynicotine:oxygen oxidoreductase

Comments:

A flavoprotein (FAD). The enzyme, which participates in nicotine degradation, is specific for the (S) isomer of 6-hydroxynicotine. The bacterium Arthrobacter nicotinovorans, in which this enzyme was originally discovered, has a different enzyme that catalyses a similar reaction with the less common (R)-isomer (cf. EC 1.5.3.6, (R)-6-hydroxynicotine oxidase).

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 37256-29-4

References:

1.	Decker, K. and Bleeg, H. Induction and purification of stereospecific nicotine oxidizing enzymes from Arthrobacter oxidans. Biochim. Biophys. Acta 105 (1965) 313–324. [PMID: 5849820]
2.	Dai, V.D., Decker, K. and Sund, H. Purification and properties of L-6-hydroxynicotine oxidase. Eur. J. Biochem. 4 (1968) 95–102. [DOI] [PMID: 5646150]
3.	Schenk, S., Hoelz, A., Krauss, B. and Decker, K. Gene structures and properties of enzymes of the plasmid-encoded nicotine catabolism of Arthrobacter nicotinovorans. J. Mol. Biol. 284 (1998) 1323–1339. [DOI] [PMID: 9878353]
4.	Qiu, J., Wei, Y., Ma, Y., Wen, R., Wen, Y. and Liu, W. A novel (S)-6-hydroxynicotine oxidase gene from Shinella sp. strain HZN7. Appl. Environ. Microbiol. 80 (2014) 5552–5560. [DOI] [PMID: 25002425]

[EC 1.5.3.5 created 1972, modified 2015]

*EC

1.5.3.6

Accepted name:

(R)-6-hydroxynicotine oxidase

Reaction:

(R)-6-hydroxynicotine + H₂O + O₂ = 1-(6-hydroxypyridin-3-yl)-4-(methylamino)butan-1-one + H₂O₂ (overall reaction)
(1a) (R)-6-hydroxynicotine + O₂ = 5-(N-methyl-4,5-dihydro-1H-pyrrol-2-yl)pyridin-2-ol + H₂O₂
(1b) 5-(N-methyl-4,5-dihydro-1H-pyrrol-2-yl)pyridin-2-ol + H₂O = 1-(6-hydroxypyridin-3-yl)-4-(methylamino)butan-1-one (spontaneous)

For diagram of nicotine catabolism by arthrobacter, click here

Glossary:

(R)-6-hydroxynicotine = 5-[(2R)-1-methylpyrrolidin-2-yl]pyridin-2-ol
5-(N-methyl-4,5-dihydro-1H-pyrrol-2-yl)pyridin-2-ol = 6-hydroxy-N-methylmyosmine
1-(6-hydroxypyridin-3-yl)-4-(methylamino)butan-1-one = 6-hydroxypseudooxynicotine

Other name(s):

D-6-hydroxynicotine oxidase; 6-hydroxy-D-nicotine oxidase

Systematic name:

(R)-6-hydroxynicotine:oxygen oxidoreductase

Comments:

A flavoprotein (FAD). The enzyme, which participates in nicotine degradation, is specific for (R) isomer of 6-hydroxynicotine, derived from the uncommon (R)-nicotine. The bacterium Arthrobacter nicotinovorans, in which this enzyme was originally discovered, has a different enzyme that catalyses a similar reaction with the (S)-isomer (cf. EC 1.5.3.5, (S)-6-hydroxynicotine oxidase).

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 37233-46-8

References:

1.	Decker, K. and Bleeg, H. Induction and purification of stereospecific nicotine oxidizing enzymes from Arthrobacter oxidans. Biochim. Biophys. Acta 105 (1965) 313–324. [PMID: 5849820]
2.	Brühmüller, M., Möhler, H.K. and Decker, K. Covalently bound flavin in D-6-hydroxynicotine oxidase from Arthrobacter oxidans. Purification and properties of D-6-hydroxynicotine oxidase. Eur. J. Biochem. 29 (1972) 143–151. [DOI] [PMID: 4628374]
3.	Brandsch, R., Hinkkanen, A.E., Mauch, L., Nagursky, H. and Decker, K. 6-Hydroxy-D-nicotine oxidase of Arthrobacter oxidans. Gene structure of the flavoenzyme and its relationship to 6-hydroxy-L-nicotine oxidase. Eur. J. Biochem. 167 (1987) 315–320. [DOI] [PMID: 3622516]
4.	Schenk, S., Hoelz, A., Krauss, B. and Decker, K. Gene structures and properties of enzymes of the plasmid-encoded nicotine catabolism of Arthrobacter nicotinovorans. J. Mol. Biol. 284 (1998) 1323–1339. [DOI] [PMID: 9878353]
5.	Koetter, J.W. and Schulz, G.E. Crystal structure of 6-hydroxy-D-nicotine oxidase from Arthrobacter nicotinovorans. J. Mol. Biol. 352 (2005) 418–428. [DOI] [PMID: 16095622]

[EC 1.5.3.6 created 1972, modified 2015]

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]

*EC

1.6.3.5

Accepted name:

renalase

Reaction:

(1) 1,2-dihydro-β-NAD(P) + H⁺ + O₂ = β-NAD(P)⁺ + H₂O₂
(2) 1,6-dihydro-β-NAD(P) + H⁺ + O₂ = β-NAD(P)⁺ + H₂O₂

Other name(s):

αNAD(P)H oxidase/anomerase (incorrect); NAD(P)H:oxygen oxidoreductase (H₂O₂-forming, epimerising) (incorrect)

Systematic name:

dihydro-NAD(P):oxygen oxidoreductase (H₂O₂-forming)

Comments:

Requires FAD. Renalase, previously thought to be a hormone, is a flavoprotein secreted into the blood by the kidney that oxidizes the 1,2-dihydro- and 1,6-dihydro- isomeric forms of β-NAD(P)H back to β-NAD(P)⁺. These isomeric forms, generated by nonspecific reduction of β-NAD(P)⁺ or by tautomerization of β-NAD(P)H, are potent inhibitors of primary metabolism dehydrogenases and pose a threat to normal respiration.

Links to other databases:

References:

1.	Xu, J., Li, G., Wang, P., Velazquez, H., Yao, X., Li, Y., Wu, Y., Peixoto, A., Crowley, S. and Desir, G.V. Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure. J. Clin. Invest. 115 (2005) 1275–1280. [DOI] [PMID: 15841207]
2.	Beaupre, B.A., Hoag, M.R., Roman, J., Forsterling, F.H. and Moran, G.R. Metabolic function for human renalase: oxidation of isomeric forms of β-NAD(P)H that are inhibitory to primary metabolism. Biochemistry 54 (2015) 795–806. [DOI] [PMID: 25531177]

[EC 1.6.3.5 created 2014, modified 2015]

1.6.5.12

Accepted name:

demethylphylloquinone reductase

Reaction:

demethylphylloquinone + NADPH + H⁺ = demethylphylloquinol + NADP⁺

Glossary:

demethylphylloquinone = 2-phytyl-1,4-naphthoquinone

Other name(s):

ndbB (gene name); NDC1 (gene name); demethylphylloquinone:NADPH oxidoreductase

Systematic name:

NADPH:demethylphylloquinone oxidoreductase

Comments:

The enzyme, found in plants and cyanobacteria, is involved in the biosynthesis of phylloquinone (vitamin K₁), an electron carrier associated with photosystem I. The enzyme is a type II NADPH dehydrogenase and requires a flavine adenine dinucleotide cofactor.

Links to other databases:

References:

Fatihi, A., Latimer, S., Schmollinger, S., Block, A., Dussault, P.H., Vermaas, W.F., Merchant, S.S. and Basset, G.J. A dedicated type II NADPH dehydrogenase performs the penultimate step in the biosynthesis of vitamin K₁ in Synechocystis and Arabidopsis. Plant Cell 27 (2015) 1730–1741. [DOI] [PMID: 26023160]

[EC 1.6.5.12 created 2015]

1.13.11.81

Accepted name:

7,8-dihydroneopterin oxygenase

Reaction:

7,8-dihydroneopterin + O₂ = 7,8-dihydroxanthopterin + formate + glycolaldehyde

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

Glossary:

7,8-dihydroneopterin = 2-amino-6-[(1S,2R)-1,2,3-trihydroxypropyl]-7,8-dihydropteridin-4(3H)-one
7,8-dihydroxanthopterin = 2-amino-3,5,7,8-tetrahydropteridin-4,6-dione

Systematic name:

7,8-dihydroneopterin:oxygen oxidoreductase

Comments:

The enzyme from the bacterium Mycobacterium tuberculosis is multifunctional and also catalyses the epimerisation of the 2′-hydroxy group of 7,8-dihydroneopterin (EC 5.1.99.8, 7,8-dihydroneopterin epimerase) and the reaction of EC 4.1.2.25 (dihydroneopterin aldolase).

Links to other databases:

References:

1.	Czekster, C.M. and Blanchard, J.S. One substrate, five products: reactions catalyzed by the dihydroneopterin aldolase from Mycobacterium tuberculosis. J. Am. Chem. Soc. 134 (2012) 19758–19771. [DOI] [PMID: 23150985]

[EC 1.13.11.81 created 2015]

1.13.11.82

Accepted name:

8′-apo-carotenoid 13,14-cleaving dioxygenase

Reaction:

8′-apo-β-carotenal + O₂ = 13-apo-β-carotenone + 2,6-dimethyldeca-2,4,6,8-tetraenedial

For diagram of 8′-apo-β-carotenal metabolites, click here

Other name(s):

NACOX1 (gene name)

Systematic name:

8′-apo-β-carotenal:oxygen 13,14-dioxygenase (bond-cleaving)

Comments:

Isolated from the bacterium Novosphingobium aromaticivorans. It is less active with 4′-apo-β-carotenal and γ-carotene.

Links to other databases:

References:

1.	Kim, Y.S., Seo, E.S. and Oh, D.K. Characterization of an apo-carotenoid 13,14-dioxygenase from Novosphingobium aromaticivorans that converts β-apo-8′-carotenal to β-apo-13-carotenone. Biotechnol. Lett. 34 (2012) 1851–1856. [DOI] [PMID: 22711425]

[EC 1.13.11.82 created 2015]

1.14.11.49

Accepted name:

uridine-5′-phosphate dioxygenase

Reaction:

UMP + 2-oxoglutarate + O₂ = 5′-dehydrouridine + succinate + CO₂ + phosphate

For diagram of pyrimidine biosynthesis, click here

Glossary:

5′-dehydrouridine = uridine-5′-aldehyde

Other name(s):

lipL (gene name)

Systematic name:

UMP,2-oxoglutarate:oxygen oxidoreductase

Comments:

The enzyme catalyses a net dephosphorylation and oxidation of UMP to generate 5′-dehydrouridine, the first intermediate in the biosynthesis of the unusual aminoribosyl moiety found in several C⁷-furanosyl nucleosides such as A-90289s, caprazamycins, liposidomycins, muraymycins and FR-900453. Requires Fe²⁺.

Links to other databases:

References:

1.	Yang, Z., Chi, X., Funabashi, M., Baba, S., Nonaka, K., Pahari, P., Unrine, J., Jacobsen, J.M., Elliott, G.I., Rohr, J. and Van Lanen, S.G. Characterization of LipL as a non-heme, Fe(II)-dependent α-ketoglutarate:UMP dioxygenase that generates uridine-5′-aldehyde during A-90289 biosynthesis. J. Biol. Chem. 286 (2011) 7885–7892. [DOI] [PMID: 21216959]
2.	Yang, Z., Unrine, J., Nonaka, K. and Van Lanen, S.G. Fe(II)-dependent, uridine-5′-monophosphate α-ketoglutarate dioxygenases in the synthesis of 5′-modified nucleosides. Methods Enzymol. 516 (2012) 153–168. [DOI] [PMID: 23034228]

[EC 1.14.11.49 created 2015]

1.14.12.21

Transferred entry:

benzoyl-CoA 2,3-dioxygenase. Now EC 1.14.13.208, benzoyl-CoA 2,3-epoxidase

[EC 1.14.12.21 created 2010, deleted 2015]

1.14.12.24

Accepted name:

2,4-dinitrotoluene dioxygenase

Reaction:

2,4-dinitrotoluene + NADH + O₂ = 4-methyl-5-nitrocatechol + nitrite + NAD⁺

Other name(s):

dntA (gene name)

Systematic name:

2,4-dinitrotoluene,NADH:oxygen oxidoreductase (4,5-hydroxylating, nitrite-releasing)

Comments:

This enzyme, characterized from the bacterium Burkholderia sp. strain DNT, is a member of the naphthalene family of bacterial Rieske non-heme iron dioxygenases. It comprises a multicomponent system, containing a Rieske [2Fe-2S] ferredoxin, an NADH-dependent flavoprotein reductase (EC 1.18.1.3, ferredoxin—NAD⁺ reductase), and an α3β3 oxygenase. The enzyme forms a cis-dihydroxylated product that spontaneously rearranges to form a catechol with accompanying release of nitrite. It does not act on nitrobenzene. cf. EC 1.14.12.23, nitroarene dioxygenase.

Links to other databases:

References:

1.	Suen, W.C., Haigler, B.E. and Spain, J.C. 2,4-Dinitrotoluene dioxygenase from Burkholderia sp. strain DNT: similarity to naphthalene dioxygenase. J. Bacteriol. 178 (1996) 4926–4934. [DOI] [PMID: 8759857]

[EC 1.14.12.24 created 2015]

1.14.13.95

Transferred entry:

7α-hydroxycholest-4-en-3-one 12α-hydroxylase. Now included with EC 1.14.14.139, 5β-cholestane-3α,7α-diol 12α-hydroxylase

[EC 1.14.13.95 created 2005, deleted 2015]

1.14.13.132

Transferred entry:

squalene monooxygenase. Now EC 1.14.14.17, squalene monooxygenase

[EC 1.14.13.132 created 1961 as EC 1.99.1.13, transferred 1965 to EC 1.14.1.3, part transferred 1972 to EC 1.14.99.7, transferred 2011 to EC 1.14.13.132, deleted 2015]

*EC

1.14.13.190

Transferred entry:

ferruginol synthase. Now EC 1.14.14.175, ferruginol synthase

[EC 1.14.13.190 created 2014, modified 2015, deleted 2020]

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]

1.14.13.207

Transferred entry:

ipsdienol synthase. Now EC 1.14.14.31, ipsdienol synthase

[EC 1.14.13.207 created 2015, deleted 2016]

1.14.13.208

Accepted name:

benzoyl-CoA 2,3-epoxidase

Reaction:

benzoyl-CoA + NADPH + H⁺ + O₂ = 2,3-epoxy-2,3-dihydrobenzoyl-CoA + NADP⁺ + H₂O

For diagram of Benzoyl-CoA catabolism, click here

Other name(s):

benzoyl-CoA dioxygenase/reductase (incorrect); BoxBA; BoxA/BoxB system; benzoyl-CoA 2,3-dioxygenase (incorrect)

Systematic name:

benzoyl-CoA,NADPH:oxygen oxidoreductase (2,3-epoxydizing)

Comments:

The enzyme is involved in aerobic benzoate metabolism in Azoarcus evansii. BoxB functions as the oxygenase part of benzoyl-CoA oxygenase in conjunction with BoxA, the reductase component, which upon binding of benzoyl-CoA, transfers two electrons to the ring in the course of monooxygenation. BoxA is a homodimeric 46 kDa iron-sulfur-flavoprotein (FAD), BoxB is a monomeric iron-protein [1].

Links to other databases:

References:

1.	Zaar, A., Gescher, J., Eisenreich, W., Bacher, A. and Fuchs, G. New enzymes involved in aerobic benzoate metabolism in Azoarcus evansii. Mol. Microbiol. 54 (2004) 223–238. [DOI] [PMID: 15458418]
2.	Gescher, J., Zaar, A., Mohamed, M., Schagger, H. and Fuchs, G. Genes coding for a new pathway of aerobic benzoate metabolism in Azoarcus evansii. J. Bacteriol. 184 (2002) 6301–6315. [DOI] [PMID: 12399500]
3.	Mohamed, M.E., Zaar, A., Ebenau-Jehle, C. and Fuchs, G. Reinvestigation of a new type of aerobic benzoate metabolism in the proteobacterium Azoarcus evansii. J. Bacteriol. 183 (2001) 1899–1908. [DOI] [PMID: 11222587]
4.	Rather, L.J., Knapp, B., Haehnel, W. and Fuchs, G. Coenzyme A-dependent aerobic metabolism of benzoate via epoxide formation. J. Biol. Chem. 285 (2010) 20615–20624. [DOI] [PMID: 20452977]

[EC 1.14.13.208 created 2010 as EC 1.14.12.21, transferred 2015 to EC 1.14.13.208]

1.14.13.209

Accepted name:

salicyloyl-CoA 5-hydroxylase

Reaction:

2-hydroxybenzoyl-CoA + NADH + H⁺ + O₂ = gentisyl-CoA + NAD⁺ + H₂O

Glossary:

2-hydroxybenzoyl-CoA = salicyloyl-CoA
gentisate = 2,5-dihydroxybenzoate

Other name(s):

sdgC (gene name)

Systematic name:

salicyloyl-CoA,NADH:oxygen oxidoreductase (5-hydroxylating)

Comments:

The enzyme, characterized from the bacterium Streptomyces sp. WA46, participates in a pathway for salicylate degradation. cf. EC 1.14.13.172, salicylate 5-hydroxylase.

Links to other databases:

References:

1.	Ishiyama, D., Vujaklija, D. and Davies, J. Novel pathway of salicylate degradation by Streptomyces sp. strain WA46. Appl. Environ. Microbiol. 70 (2004) 1297–1306. [DOI] [PMID: 15006746]

[EC 1.14.13.209 created 2015]

*EC

1.14.14.1

Accepted name:

unspecific monooxygenase

Reaction:

RH + [reduced NADPH—hemoprotein reductase] + O₂ = ROH + [oxidized NADPH—hemoprotein reductase] + H₂O

Other name(s):

microsomal monooxygenase; xenobiotic monooxygenase; aryl-4-monooxygenase; aryl hydrocarbon hydroxylase; microsomal P-450; flavoprotein-linked monooxygenase; flavoprotein monooxygenase; substrate,reduced-flavoprotein:oxygen oxidoreductase (RH-hydroxylating or -epoxidizing)

Systematic name:

substrate,NADPH—hemoprotein reductase:oxygen oxidoreductase (RH-hydroxylating or -epoxidizing)

Comments:

A group of P-450 heme-thiolate proteins, acting on a wide range of substrates including many xenobiotics, steroids, fatty acids, vitamins and prostaglandins; reactions catalysed include hydroxylation, epoxidation, N-oxidation, sulfooxidation, N-, S- and O-dealkylations, desulfation, deamination, and reduction of azo, nitro and N-oxide groups. Together with EC 1.6.2.4, NADPH—hemoprotein reductase, it forms a system in which two reducing equivalents are supplied by NADPH. Some of the reactions attributed to EC 1.14.15.3, alkane 1-monooxygenase, belong here.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 9038-14-6

References:

1.	Booth, J. and Boyland, E. The biochemistry of aromatic amines. 3. Enzymic hydroxylation by rat-liver microsomes. Biochem. J. 66 (1957) 73–78. [PMID: 13426111]
2.	Fujita, T. and Mannering, G.J. Differences in soluble P-450 hemoproteins from livers of rats treated with phenobarbital and 3-methylcholanthrene. Chem. Biol. Interact. 3 (1971) 264–265. [DOI] [PMID: 5132997]
3.	Haugen, D.A. and Coon, M.J. Properties of electrophoretically homogeneous phenobarbital-inducible and β-naphthoflavone-inducible forms of liver microsomal cytochrome P-450. J. Biol. Chem. 251 (1976) 7929–7939. [PMID: 187601]
4.	Imaoka, S., Inoue, K. and Funae, Y. Aminopyrine metabolism by multiple forms of cytochrome P-450 from rat liver microsomes: simultaneous quantitation of four aminopyrine metabolites by high-performance liquid chromatography. Arch. Biochem. Biophys. 265 (1988) 159–170. [DOI] [PMID: 3415241]
5.	Johnson, E.F., Zounes, M. and Müller-Eberhard, U. Characterization of three forms of rabbit microsomal cytochrome P-450 by peptide mapping utilizing limited proteolysis in sodium dodecyl sulfate and analysis by gel electrophoresis. Arch. Biochem. Biophys. 192 (1979) 282–289. [DOI] [PMID: 434823]
6.	Kupfer, D., Miranda, G.K., Navarro, J., Piccolo, D.E. and Theoharides, A.D. Effect of inducers and inhibitors of monooxygenase on the hydroxylation of prostaglandins in the guinea pig. Evidence for several monooxygenases catalyzing ω- and ω-1-hydroxylation. J. Biol. Chem. 254 (1979) 10405–10414. [PMID: 489601]
7.	Lang, M.A., Gielen, J.E. and Nebert, D.W. Genetic evidence for many unique liver microsomal P-450-mediated monooxygenase activities in heterogeneic stock mice. J. Biol. Chem. 256 (1981) 12068–12075. [PMID: 7298645]
8.	Lang, M.A. and Nebert, D.W. Structural gene products of the Ah locus. Evidence for many unique P-450-mediated monooxygenase activities reconstituted from 3-methylcholanthrene-treated C57BL/6N mouse liver microsomes. J. Biol. Chem. 256 (1981) 12058–12075. [PMID: 7298644]
9.	Leo, M.A., Lasker, J.M., Rauby, J.L., Kim, C.I., Black, M. and Lieber, C.S. Metabolism of retinol and retinoic acid by human liver cytochrome P₄₅₀IIC8. Arch. Biochem. Biophys. 269 (1989) 305–312. [DOI] [PMID: 2916844]
10.	Lu, A.Y.H., Kuntzman, S.W., Jacobson, M. and Conney, A.H. Reconstituted liver microsomal enzyme system that hydroxylates drugs, other foreign compounds, and endogenous substrates. II. Role of the cytochrome P-450 and P-448 fractions in drug and steroid hydroxylations. J. Biol. Chem. 247 (1972) 1727–1734. [PMID: 4401153]
11.	Mitoma, C., Posner, H.S., Reitz, H.C. and Udenfriend, S. Enzymic hydroxylation of aromatic compounds. Arch. Biochem. Biophys. 61 (1956) 431–441. [DOI] [PMID: 13314626]
12.	Mitoma, C. and Udenfriend, S. Aryl-4-hydroxylase. Methods Enzymol. 5 (1962) 816–819.
13.	Napoli, J.L., Okita, R.T., Masters, B.S. and Horst, R.L. Identification of 25,26-dihydroxyvitamin D₃ as a rat renal 25-hydroxyvitamin D₃ metabolite. Biochemistry 20 (1981) 5865–5871. [PMID: 7295706]
14.	Nebert, D.W. and Gelboin, H.V. Substrate-inducible microsomal aryl hydroxylase in mammalian cell culture. I. Assay and properties of induced enzyme. J. Biol. Chem. 243 (1968) 6242–6249. [PMID: 4387094]
15.	Suhara, K., Ohashi, K., Takahashi, K. and Katagiri, M. Aromatase and nonaromatizing 10-demethylase activity of adrenal cortex mitochondrial P-450(11)beta. Arch. Biochem. Biophys. 267 (1988) 31–37. [DOI] [PMID: 3264134]
16.	Theoharides, A.D. and Kupfer, D. Evidence for different hepatic microsomal monooxygenases catalyzing ω- and (ω-1)-hydroxylations of prostaglandins E1 and E2. Effects of inducers of monooxygenase on the kinetic constants of prostaglandin hydroxylation. J. Biol. Chem. 256 (1981) 2168–2175. [PMID: 7462235]
17.	Thomas, P.E., Lu, A.Y.H., Ryan, D., West, S.B., Kawalek, J. and Levin, W. Immunochemical evidence for six forms of rat liver cytochrome P₄₅₀ obtained using antibodies against purified rat liver cytochromes P₄₅₀ and P448. Mol. Pharmacol. 12 (1976) 746–758. [PMID: 825720]

[EC 1.14.14.1 created 1961 as EC 1.99.1.1, transferred 1965 to EC 1.14.1.1, transferred 1972 to EC 1.14.14.1 (EC 1.14.14.2 created 1972, incorporated 1976, EC 1.14.99.8 created 1972, incorporated 1984), modified 2015]

1.14.14.16

Accepted name:

steroid 21-monooxygenase

Reaction:

a C₂₁ steroid + [reduced NADPH—hemoprotein reductase] + O₂ = a 21-hydroxy-C₂₁-steroid + [oxidized NADPH—hemoprotein reductase] + H₂O

Other name(s):

steroid 21-hydroxylase; 21-hydroxylase; P450c21; CYP21A2 (gene name)

Systematic name:

steroid,NADPH—hemoprotein reductase:oxygen oxidoreductase (21-hydroxylating)

Comments:

A P-450 heme-thiolate protein responsible for the conversion of progesterone and 17α-hydroxyprogesterone to their respective 21-hydroxylated derivatives, 11-deoxycorticosterone and 11-deoxycortisol. Involved in the biosynthesis of the hormones aldosterone and cortisol. The electron donor is EC 1.6.2.4, NADPH—hemoprotein reductase.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9029-68-9

References:

1.	Hayano, M. and Dorfman, R.I. The action of adrenal homogenates on progesterone, 17-hydroxyprogesterone and 21-desoxycortisone. Arch. Biochem. Biophys. 36 (1952) 237–239. [DOI] [PMID: 14934270]
2.	Plager, J.E. and Samuels, L.T. Synthesis of C14-17-hydroxy-11-desoxycorticosterone and 17-hydroxycorticosterone by fractionated extracts of adrenal homogenates. Arch. Biochem. Biophys. 42 (1953) 477–478. [DOI] [PMID: 13031650]
3.	Ryan, K.J. and Engel, L.L. Hydroxylation of steroids at carbon 21. J. Biol. Chem. 225 (1957) 103–114. [PMID: 13416221]
4.	Kominami, S., Ochi, H., Kobayashi, Y. and Takemori, S. Studies on the steroid hydroxylation system in adrenal cortex microsomes. Purification and characterization of cytochrome P-450 specific for steroid C-21 hydroxylation. J. Biol. Chem. 255 (1980) 3386–3394. [PMID: 6767716]
5.	Martineau, I., Belanger, A., Tchernof, A. and Tremblay, Y. Molecular cloning and expression of guinea pig cytochrome P450c21 cDNA (steroid 21-hydroxylase) isolated from the adrenals. J. Steroid Biochem. Mol. Biol. 86 (2003) 123–132. [DOI] [PMID: 14568563]
6.	Arase, M., Waterman, M.R. and Kagawa, N. Purification and characterization of bovine steroid 21-hydroxylase (P450c21) efficiently expressed in Escherichia coli. Biochem. Biophys. Res. Commun. 344 (2006) 400–405. [DOI] [PMID: 16597434]

[EC 1.14.14.16 created 1961 as EC 1.99.1.11, transferred 1965 to EC 1.14.1.8, transferred 1972 to EC 1.14.99.10, modified 2013, transferred 2015 to EC 1.14.14.16]

1.14.14.17

Accepted name:

squalene monooxygenase

Reaction:

squalene + [reduced NADPH—hemoprotein reductase] + O₂ = (3S)-2,3-epoxy-2,3-dihydrosqualene + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of α-onocerin biosynthesis, click here and for diagram of triterpenoid biosynthesis, click here

Other name(s):

squalene epoxidase; squalene-2,3-epoxide cyclase; squalene 2,3-oxidocyclase; squalene hydroxylase; squalene oxydocyclase; squalene-2,3-epoxidase

Systematic name:

squalene,NADPH—hemoprotein:oxygen oxidoreductase (2,3-epoxidizing)

Comments:

A flavoprotein (FAD). This enzyme, together with EC 5.4.99.7, lanosterol synthase, was formerly known as squalene oxidocyclase. The electron donor is EC 1.6.2.4, NADPH—hemoprotein reductase [5,7].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9029-62-3

References:

1.	Corey, E.J., Russey, W.E. and Ortiz de Montellano, P.R. 2,3-Oxidosqualene, an intermediate in the biological synthesis of sterols from squalene. J. Am. Chem. Soc. 88 (1966) 4750–4751. [PMID: 5918046]
2.	Tchen, T.T. and Bloch, K. On the conversion of squalene to lanosterol in vitro. J. Biol. Chem. 226 (1957) 921–930. [PMID: 13438881]
3.	van Tamelen, E.E., Willett, J.D., Clayton, R.B. and Lord, K.E. Enzymic conversion of squalene 2,3-oxide to lanosterol and cholesterol. J. Am. Chem. Soc. 88 (1966) 4752–4754. [PMID: 5918048]
4.	Yamamoto, S. and Bloch, K. Studies on squalene epoxidase of rat liver. J. Biol. Chem. 245 (1970) 1670–1674. [PMID: 5438357]
5.	Ono, T. and Bloch, K. Solubilization and partial characterization of rat liver squalene epoxidase. J. Biol. Chem. 250 (1975) 1571–1579. [PMID: 234459]
6.	Satoh, T., Horie, M., Watanabe, H., Tsuchiya, Y. and Kamei, T. Enzymatic properties of squalene epoxidase from Saccharomyces cerevisiae. Biol. Pharm. Bull. 16 (1993) 349–352. [PMID: 8358382]
7.	Chugh, A., Ray, A. and Gupta, J.B. Squalene epoxidase as hypocholesterolemic drug target revisited. Prog. Lipid Res. 42 (2003) 37–50. [DOI] [PMID: 12467639]
8.	He, F., Zhu, Y., He, M. and Zhang, Y. Molecular cloning and characterization of the gene encoding squalene epoxidase in Panax notoginseng. DNA Seq 19 (2008) 270–273. [DOI] [PMID: 17852349]

[EC 1.14.14.17 created 1961 as EC 1.99.1.13, transferred 1965 to EC 1.14.1.3, part transferred 1972 to EC 1.14.99.7, transferred 2011 to EC 1.14.13.132, transferred 2015 to EC 1.14.14.17]

1.14.14.18

Accepted name:

heme oxygenase (biliverdin-producing)

Reaction:

protoheme + 3 [reduced NADPH—hemoprotein reductase] + 3 O₂ = biliverdin + Fe²⁺ + CO + 3 [oxidized NADPH—hemoprotein reductase] + 3 H₂O

For diagram of the reaction mechanism, click here

Other name(s):

ORP33 proteins; haem oxygenase (ambiguous); heme oxygenase (decyclizing) (ambiguous); heme oxidase (ambiguous); haem oxidase (ambiguous); heme oxygenase (ambiguous); heme,hydrogen-donor:oxygen oxidoreductase (α-methene-oxidizing, hydroxylating)

Systematic name:

protoheme,NADPH—hemoprotein reductase:oxygen oxidoreductase (α-methene-oxidizing, hydroxylating)

Comments:

This mammalian enzyme participates in the degradation of heme. The terminal oxygen atoms that are incorporated into the carbonyl groups of pyrrole rings A and B of biliverdin are derived from two separate oxygen molecules [4]. The third oxygen molecule provides the oxygen atom that converts the α-carbon to CO. The enzyme requires NAD(P)H and EC 1.6.2.4, NADPH—hemoprotein reductase. cf. EC 1.14.15.20, heme oxygenase (biliverdin-producing, ferredoxin).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9059-22-7

References:

1.	Maines, M.D., Ibrahim, N.G. and Kappas, K. Solubilization and partial purification of heme oxygenase from rat liver. J. Biol. Chem. 252 (1977) 5900–5903. [PMID: 18477]
2.	Sunderman, F.W., Jr., Downs, J.R., Reid, M.C. and Bibeau, L.M. Gas-chromatographic assay for heme oxygenase activity. Clin. Chem. 28 (1982) 2026–2032. [PMID: 6897023]
3.	Yoshida, T., Takahashi, S. and Kikuchi, J. Partial purification and reconstitution of the heme oxygenase system from pig spleen microsomes. J. Biochem. (Tokyo) 75 (1974) 1187–1191. [PMID: 4370250]
4.	Noguchi, M., Yoshida, T. and Kikuchi, G. Specific requirement of NADPH-cytochrome c reductase for the microsomal heme oxygenase reaction yielding biliverdin IX α. FEBS Lett. 98 (1979) 281–284. [DOI] [PMID: 105935]
5.	Lad, L., Schuller, D.J., Shimizu, H., Friedman, J., Li, H., Ortiz de Montellano, P.R. and Poulos, T.L. Comparison of the heme-free and -bound crystal structures of human heme oxygenase-1. J. Biol. Chem. 278 (2003) 7834–7843. [DOI] [PMID: 12500973]

[EC 1.14.14.18 created 1972 as EC 1.14.99.3, modified 2006, transferred 2015 to EC 1.14.14.18, modified 2016]

1.14.14.19

Accepted name:

steroid 17α-monooxygenase

Reaction:

a C₂₁-steroid + [reduced NADPH—hemoprotein reductase] + O₂ = a 17α-hydroxy-C₂₁-steroid + [oxidized NADPH—hemoprotein reductase] + H₂O

Other name(s):

steroid 17α-hydroxylase; cytochrome P-450 17α; cytochrome P-450 (P-450 17α,lyase); 17α-hydroxylase-C17,20 lyase; CYP17; CYP17A1 (gene name)

Systematic name:

steroid,NADPH—hemoprotein reductase:oxygen oxidoreductase (17α-hydroxylating)

Comments:

Requires NADPH and EC 1.6.2.4, NADPH—hemoprotein reductase. A microsomal hemeprotein that catalyses two independent reactions at the same active site - the 17α-hydroxylation of pregnenolone and progesterone, which is part of glucocorticoid hormones biosynthesis, and the conversion of the 17α-hydroxylated products via a 17,20-lyase reaction to form androstenedione and dehydroepiandrosterone, leading to sex hormone biosynthesis (EC 1.14.14.32, 17α-hydroxyprogesterone deacetylase). The ratio of the 17α-hydroxylase and 17,20-lyase activities is an important factor in determining the directions of steroid hormone biosynthesis towards biosynthesis of glucocorticoid or sex hormones.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9029-67-8

References:

1.	Lynn, W.S. and Brown, R.H. The conversion of progesterone to androgens by testes. J. Biol. Chem. 232 (1958) 1015–1030. [PMID: 13549484]
2.	Yoshida, K.-I., Oshima, H. and Troen, P. Studies of the human testis. XIII. Properties of nicotinamide adenine dinucleotide (reduced form)-linked 17α-hydroxylation. J. Clin. Endocrinol. Metab. 50 (1980) 895–899. [DOI] [PMID: 6966286]
3.	Gilep, A.A., Estabrook, R.W. and Usanov, S.A. Molecular cloning and heterologous expression in E. coli of cytochrome P45017α. Comparison of structural and functional properties of substrate-specific cytochromes P450 from different species. Biochemistry (Mosc.) 68 (2003) 86–98. [PMID: 12693981]
4.	Kolar, N.W., Swart, A.C., Mason, J.I. and Swart, P. Functional expression and characterisation of human cytochrome P45017α in Pichia pastoris. J. Biotechnol. 129 (2007) 635–644. [DOI] [PMID: 17386955]
5.	Pechurskaya, T.A., Lukashevich, O.P., Gilep, A.A. and Usanov, S.A. Engineering, expression, and purification of "soluble" human cytochrome P45017α and its functional characterization. Biochemistry (Mosc.) 73 (2008) 806–811. [PMID: 18707589]

[EC 1.14.14.19 created 1961 as EC 1.99.1.9, transferred 1965 to EC 1.14.1.7, transferred 1972 to EC 1.14.99.9, modified 2013, transferred 2015 to EC 1.14.14.19]

1.14.15.14

Accepted name:

methyl-branched lipid ω-hydroxylase

Reaction:

a methyl-branched lipid + O₂ + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ = an ω-hydroxy-methyl-branched lipid + H₂O + 2 oxidized ferredoxin [iron-sulfur] cluster

Other name(s):

CYP124

Systematic name:

methyl-branched lipid,reduced-ferredoxin:oxygen oxidoreductase (ω-hydroxylating)

Comments:

The enzyme, found in pathogenic and nonpathogenic mycobacteria species, actinomycetes, and some proteobacteria, hydroxylates the ω-carbon of a number of methyl-branched lipids, including (2E,6E)-farnesol, phytanate, geranylgeraniol, 15-methylpalmitate and (2E,6E)-farnesyl diphosphate. It is a P-450 heme-thiolate enzyme.

Links to other databases:

References:

1.	Johnston, J.B., Kells, P.M., Podust, L.M. and Ortiz de Montellano, P.R. Biochemical and structural characterization of CYP124: a methyl-branched lipid ω-hydroxylase from Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 106 (2009) 20687–20692. [DOI] [PMID: 19933331]

[EC 1.14.15.14 created 2015]

1.14.18.8

Transferred entry:

7α-hydroxycholest-4-en-3-one 12α-hydroxylase. Now included with EC 1.14.14.139, 5β-cholestane-3α,7α-diol 12α-hydroxylase

[EC 1.14.18.8 created 2005 as EC 1.14.13.95, transferred 2015 to EC 1.14.18.8, deleted 2020]

*EC

1.14.19.4

Accepted name:

acyl-lipid (11-3)-desaturase

Reaction:

(1) an (11Z,14Z)-icosa-11,14-dienoyl-[glycerolipid] + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = an (8Z,11Z,14Z)-icosa-8,11,14-trienoyl-[glycerolipid] + 2 ferricytochrome b₅ + 2 H₂O
(2) an (11Z,14Z,17Z)-icosa-11,14,17-trienoyl-[glycerolipid] + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = an (8Z,11Z,14Z,17Z)-icosa-8,11,14,17-tetraenoyl-[glycerolipid] + 2 ferricytochrome b₅ + 2 H₂O

Glossary:

di-homo-γ-linolenate = (8Z,11Z,14Z)-icosa-8,11,14-trienoate

Other name(s):

acyl-lipid 8-desaturase; Δ⁸ fatty acid desaturase; Δ⁸-desaturase; Δ⁸-fatty-acid desaturase; efd1 (gene name); D8Des (gene name); phytosphinganine,hydrogen donor:oxygen Δ⁸-oxidoreductase (incorrect); SLD

Systematic name:

acyl-lipid,ferrocytochrome b₅:oxygen oxidoreductase [(11-3),(11-2)-cis-dehydrogenating]

Comments:

The enzyme, characterized from the protist Euglena gracilis [1] and the microalga Rebecca salina [2], introduces a cis double bond at the 8-position in 20-carbon fatty acids that are incorporated into a glycerolipid and have an existing Δ¹¹ desaturation. The enzyme is a front-end desaturase, introducing the new double bond between the pre-existing double bond and the carboxyl-end of the fatty acid. It contains a cytochrome b₅ domain that acts as the direct electron donor to the active site of the desaturase, and does not require an external cytochrome. Involved in alternative pathways for the biosynthesis of the polyunsaturated fatty acids arachidonate and icosapentaenoate.

Links to other databases:

References:

1.	Wallis, J.G. and Browse, J. The Δ⁸-desaturase of Euglena gracilis: an alternate pathway for synthesis of 20-carbon polyunsaturated fatty acids. Arch. Biochem. Biophys. 365 (1999) 307–316. [DOI] [PMID: 10328826]
2.	Zhou, X.R., Robert, S.S., Petrie, J.R., Frampton, D.M., Mansour, M.P., Blackburn, S.I., Nichols, P.D., Green, A.G. and Singh, S.P. Isolation and characterization of genes from the marine microalga Pavlova salina encoding three front-end desaturases involved in docosahexaenoic acid biosynthesis. Phytochemistry 68 (2007) 785–796. [DOI] [PMID: 17291553]

[EC 1.14.19.4 created 2008, modified 2015]

*EC

1.14.19.6

Accepted name:

acyl-CoA (9+3)-desaturase

Reaction:

(1) oleoyl-CoA + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = linoleoyl-CoA + 2 ferricytochrome b₅ + 2 H₂O
(2) palmitoleoyl-CoA + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = (9Z,12Z)-hexadeca-9,12-dienoyl-CoA + 2 ferricytochrome b₅ + 2 H₂O

Glossary:

oleoyl-CoA = cis-octadec-9-enoyl-CoA = (9Z)-octadec-9-enoyl-CoA = 18:1 cis-9 = 18:1(n-9)
linoleoyl-CoA = cis,cis-octadeca-9,12-dienoyl-CoA = (9Z,12Z)-octadeca-9,12-dienoyl-CoA = 18:2(n-6)
palmitoleoyl-CoA = (9Z)-hexadec-9-enoyl-CoA

Other name(s):

oleoyl-CoA 12-desaturase; Δ¹² fatty acid desaturase; Δ¹²(ω⁶)-desaturase; oleoyl-CoA Δ¹² desaturase; Δ¹² desaturase; Δ¹²-desaturase; Δ¹²-fatty-acid desaturase; acyl-CoA,hydrogen donor:oxygen Δ¹²-oxidoreductase

Systematic name:

acyl-CoA,ferrocytochrome b₅:oxygen oxidoreductase (12,13 cis-dehydrogenating)

Comments:

This microsomal enzyme introduces a cis double bond at position 12 of fatty-acyl-CoAs that contain a cis double bond at position 9. When acting on 19:1Δ¹⁰ fatty acyl-CoA the enzyme from the pathogenic protozoan Trypanosoma brucei introduces the new double bond at position 13, indicating that the new double bond is introduced three carbons from the existing cis double bond, towards the methyl-end of the fatty acid. Requires cytochrome b₅ as the electron donor [4].

Links to other databases:

References:

1.	Borgeson, C.E., de Renobales, M. and Blomquist, G.J. Characterization of the Δ¹² desaturase in the American cockroach, Periplaneta americana: the nature of the substrate. Biochim. Biophys. Acta 1047 (1990) 135–140. [DOI] [PMID: 2248971]
2.	Lomascolo, A., Dubreucq, E. and Galzy, P. Study of the Δ¹²-desaturase system of Lipomyces starkeyi. Lipids 31 (1996) 253–259. [DOI] [PMID: 8900454]
3.	Tocher, D.R., Leaver, M.J. and Hodgson, P.A. Recent advances in the biochemistry and molecular biology of fatty acyl desaturases. Prog. Lipid Res. 37 (1998) 73–117. [DOI] [PMID: 9829122]
4.	Petrini, G.A., Altabe, S.G. and Uttaro, A.D. Trypanosoma brucei oleate desaturase may use a cytochrome b₅-like domain in another desaturase as an electron donor. Eur. J. Biochem. 271 (2004) 1079–1086. [PMID: 15009186]

[EC 1.14.19.6 created 2008, modified 2015]

1.14.19.37

Accepted name:

acyl-CoA 5-desaturase

Reaction:

(1) (11Z,14Z)-icosa-11,14-dienoyl-CoA + reduced acceptor + O₂ = (5Z,11Z,14Z)-icosa-5,11,14-trienoyl-CoA + acceptor + 2 H₂O
(2) (11Z,14Z,17Z)-icosa-11,14,17-trienoyl-CoA + reduced acceptor + O₂ = (5Z,11Z,14Z,17Z)-icosa-5,11,14,17-tetraenoyl-CoA + acceptor + 2 H₂O

Glossary:

(5Z,11Z,14Z)-icosa-5,11,14-trienoate = sciadonate
(5Z,11Z,14Z,17Z)-icosa-5,11,14,17-tetraenoate = juniperonate

Other name(s):

acyl-CoA 5-desaturase (non-methylene-interrupted)

Systematic name:

acyl-CoA,acceptor:oxygen oxidoreductase (5,6 cis-dehydrogenating)

Comments:

The enzyme, characterized from the plant Anemone leveillei, introduces a cis double bond at carbon 5 of acyl-CoAs that do not contain a double bond at position 8. In vivo it forms non-methylene-interrupted polyunsaturated fatty acids such as sciadonate and juniperonate. When expressed in Arabidopsis thaliana the enzyme could also act on unsaturated substrates such as palmitoyl-CoA. cf. EC 1.14.19.44, acyl-CoA (8-3)-desaturase.

Links to other databases:

References:

Sayanova, O., Haslam, R., Venegas Caleron, M. and Napier, J.A. Cloning and characterization of unusual fatty acid desaturases from Anemone leveillei: identification of an acyl-coenzyme A C₂₀ Δ⁵-desaturase responsible for the synthesis of sciadonic acid. Plant Physiol. 144 (2007) 455–467. [DOI] [PMID: 17384161]

[EC 1.14.19.37 created 2015]

1.14.19.38

Accepted name:

acyl-lipid Δ⁶-acetylenase

Reaction:

(1) a γ-linolenoyl-[glycerolipid] + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = a (9Z,12Z)-octadeca-9,12-dien-6-ynoyl-[glycerolipid] + 2 ferricytochrome b₅ + 2 H₂O
(2) a stearidonoyl-[glycerolipid] + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = a (9Z,12Z,15Z)-octadeca-9,12,15-trien-6-ynoyl-[glycerolipid] + 2 ferricytochrome b₅ + 2 H₂O

Glossary:

γ-linolenoate = (6Z,9Z,12Z)-octadeca-6,9,12-trienoate
stearidonate = (6Z,9Z,12Z,15Z)-octadeca-6,9,12,15-tetraenoate
dicranin = (9Z,12Z,15Z)-octadeca-9,12,15-trien-6-ynoic acid

Systematic name:

Δ⁶ acyl-lipid,ferrocytochrome-b₅:oxygen oxidoreductase (6,7-dehydrogenating)

Comments:

The enzyme, characterized from the moss Ceratodon purpureus, converts the double bond at position 6 of γ-linolenate and stearidonate into a triple bond. The product of the latter, dicranin, is the main fatty acid found in C. purpureus. The enzyme contains a cytochrome b₅ domain that acts as the direct electron donor to the desaturase active site. The enzyme also has the activity of EC 1.14.19.47, acyl-lipid (9-3)-desaturase.

Links to other databases:

References:

1.	Sperling, P., Lee, M., Girke, T., Zähringer, U., Stymne, S. and Heinz, E. A bifunctional Δ⁶-fatty acyl acetylenase/desaturase from the moss Ceratodon purpureus. A new member of the cytochrome b₅ superfamily. Eur. J. Biochem. 267 (2000) 3801–3811. [DOI] [PMID: 10848999]

[EC 1.14.19.38 created 2015]

1.14.19.39

Accepted name:

acyl-lipid Δ¹²-acetylenase

Reaction:

linoleoyl-[glycerolipid] + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = crepenynyl-[glycerolipid] + 2 ferricytochrome b₅ + 2 H₂O

Glossary:

crepenynate = (9Z)-octadec-9-en-12-ynoate

Systematic name:

Δ¹² acyl-lipid,ferrocytochrome-b₅:oxygen oxidoreductase (12,13-dehydrogenating)

Comments:

The enzyme, characterized from the plant Crepis alpina, converts the double bond at position 12 of linoleate into a triple bond. The product is the main fatty acid found in triacylglycerols in the seed oil of Crepis alpina.

Links to other databases:

References:

1.	Banas, A., Bafor, M., Wiberg, E., Lenman, M., Staahl, U. and Stymne, S. Biosynthesis of an acetylenic fatty acid in microsomal preparations from developing seeds Crepis alpina. Physiol. Biochem. Mol. Biol. Plant. [Proc. Int. Symp. Plant Lipids] 12th (1997) 57–59.
2.	Lee, M., Lenman, M., Banas, A., Bafor, M., Singh, S., Schweizer, M., Nilsson, R., Liljenberg, C., Dahlqvist, A., Gummeson, P.O., Sjodahl, S., Green, A. and Stymne, S. Identification of non-heme di-iron proteins that catalyze triple bond and epoxy group formation. Science 280 (1998) 915–918. [DOI] [PMID: 9572738]
3.	Nam, J.W. and Kappock, T.J. Cloning and transcriptional analysis of Crepis alpina fatty acid desaturases affecting the biosynthesis of crepenynic acid. J. Exp. Bot. 58 (2007) 1421–1432. [DOI] [PMID: 17329262]

[EC 1.14.19.39 created 2000 as EC 1.14.99.33, transferred 2015 to EC 1.14.19.39]

1.14.19.40

Accepted name:

hex-5-enoyl-[acyl-carrier protein] acetylenase

Reaction:

hex-5-enoyl-[acyl-carrier protein] + 2 reduced ferredoxin [iron-sulfur] cluster + O₂ + 2 H⁺ = hex-5-ynoyl-[acyl-carrier protein] + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H₂O

Other name(s):

jamB (gene name)

Systematic name:

hex-5-enoyl-[acyl-carrier protein],reduced ferredoxin:oxygen oxidoreductase (5,6-dehydrogenating)

Comments:

The enzyme, characterized from the marine cyanobacterium Moorea producens, is involved in production of the ion channel blocker jamaicamide A. It is specific for hexanoate or hex-5-enoate loaded onto a dedicated acyl-carrier protein (JamC), which is encoded by a gene in the same operon.

Links to other databases:

References:

1.	Zhu, X., Liu, J. and Zhang, W. De novo biosynthesis of terminal alkyne-labeled natural products. Nat. Chem. Biol. 11 (2015) 115–120. [DOI] [PMID: 25531891]

[EC 1.14.19.40 created 2015]

1.14.19.41

Accepted name:

sterol 22-desaturase

Reaction:

ergosta-5,7,24(28)-trien-3β-ol + NADPH + H⁺ + O₂ = ergosta-5,7,22,24(28)-tetraen-3β-ol + NADP⁺ + 2 H₂O

For diagram of sterol sidechain modification, click here

Other name(s):

ERG5 (gene name); CYP710A (gene name)

Systematic name:

ergosta-5,7,24(28)-trien-3β-ol,NADPH:oxygen oxidoreductase (22,23-dehydrogenating)

Comments:

A heme-thiolate protein (P-450). The enzyme, found in yeast and plants, catalyses the introduction of a double bond between the C-22 and C-23 carbons of certain sterols. In yeast the enzyme acts on ergosta-5,7,24(28)-trien-3β-ol, a step in the biosynthesis of ergosterol. The enzyme from the plant Arabidopsis thaliana acts on sitosterol and 24-epi-campesterol, producing stigmasterol and brassicasterol, respectively.

Links to other databases:

References:

1.	Kelly, S.L., Lamb, D.C., Corran, A.J., Baldwin, B.C., Parks, L.W. and Kelly, D.E. Purification and reconstitution of activity of Saccharomyces cerevisiae P450 61, a sterol Δ²²-desaturase. FEBS Lett. 377 (1995) 217–220. [DOI] [PMID: 8543054]
2.	Skaggs, B.A., Alexander, J.F., Pierson, C.A., Schweitzer, K.S., Chun, K.T., Koegel, C., Barbuch, R. and Bard, M. Cloning and characterization of the Saccharomyces cerevisiae C-22 sterol desaturase gene, encoding a second cytochrome P-450 involved in ergosterol biosynthesis. Gene 169 (1996) 105–109. [DOI] [PMID: 8635732]
3.	Morikawa, T., Mizutani, M., Aoki, N., Watanabe, B., Saga, H., Saito, S., Oikawa, A., Suzuki, H., Sakurai, N., Shibata, D., Wadano, A., Sakata, K. and Ohta, D. Cytochrome P450 CYP710A encodes the sterol C-22 desaturase in Arabidopsis and tomato. Plant Cell 18 (2006) 1008–1022. [DOI] [PMID: 16531502]

[EC 1.14.19.41 created 2015]

1.14.19.42

Accepted name:

palmitoyl-[glycerolipid] 7-desaturase

Reaction:

a 1-acyl-2-palmitoyl-[glycerolipid] + 2 reduced ferredoxin [iron-sulfur] cluster + O₂ + 2 H⁺ = a 1-acyl-2-[(7Z)-hexadec-7-enoyl]-[glycerolipid] + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H₂O

Other name(s):

FAD5

Systematic name:

1-acyl-2-palmitoyl-[glycerolipid],ferredoxin:oxygen oxidoreductase (7,8-cis-dehydrogenating)

Comments:

The enzyme introduces a cis double bond at carbon 7 of a palmitoyl group attached to the sn-2 position of glycerolipids. The enzyme from the plant Arabidopsis thaliana is specific for palmitate in monogalactosyldiacylglycerol.

Links to other databases:

References:

1.	Kunst, L., Browse, J., Somerville, C.R. A mutant of Arabidopsis deficient in desaturation of palmitic acid in leaf lipids. Plant Physiol. 90 (1989) 943–947. [PMID: 16666902]
2.	Heilmann, I., Mekhedov, S., King, B., Browse, J. and Shanklin, J. Identification of the Arabidopsis palmitoyl-monogalactosyldiacylglycerol Δ⁷-desaturase gene FAD5, and effects of plastidial retargeting of Arabidopsis desaturases on the fad5 mutant phenotype. Plant Physiol. 136 (2004) 4237–4245. [DOI] [PMID: 15579662]

[EC 1.14.19.42 created 2015]

1.14.19.43

Accepted name:

palmitoyl-[glycerolipid] 3-(E)-desaturase

Reaction:

a 1-acyl-2-palmitoyl-[glycerolipid] + 2 reduced ferredoxin [iron-sulfur] cluster + O₂ + 2 H⁺ = a 1-acyl-2-[(3E)-hexadec-3-enoyl]-[glycerolipid] + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H₂O

Other name(s):

FAD4

Systematic name:

1-acyl-2-palmitoyl-[glycerolipid],ferredoxin:oxygen oxidoreductase (3,4-trans -dehydrogenating)

Comments:

The enzyme introduces an unusual trans double bond at carbon 3 of a palmitoyl group attached to the sn-2 position of glycerolipids. The enzyme from the plant Arabidopsis thaliana is specific for palmitate in phosphatidylglycerol. The enzyme from tobacco can also accept oleate and α-linolenate if present at the sn-2 position of phosphatidylglycerol [1].

Links to other databases:

References:

1.	Fritz, M., Lokstein, H., Hackenberg, D., Welti, R., Roth, M., Zähringer, U., Fulda, M., Hellmeyer, W., Ott, C., Wolter, F.P. and Heinz, E. Channeling of eukaryotic diacylglycerol into the biosynthesis of plastidial phosphatidylglycerol. J. Biol. Chem. 282 (2007) 4613–4625. [DOI] [PMID: 17158889]
2.	Gao, J., Ajjawi, I., Manoli, A., Sawin, A., Xu, C., Froehlich, J.E., Last, R.L. and Benning, C. FATTY ACID DESATURASE4 of Arabidopsis encodes a protein distinct from characterized fatty acid desaturases. Plant J. 60 (2009) 832–839. [DOI] [PMID: 19682287]

[EC 1.14.19.43 created 2015]

1.14.19.44

Accepted name:

acyl-CoA (8-3)-desaturase

Reaction:

(1) (8Z,11Z,14Z)-icosa-8,11,14-trienoyl-CoA + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = arachidonoyl-CoA + 2 ferricytochrome b₅ + 2 H₂O
(2) (8Z,11Z,14Z,17Z)-icosa-8,11,14,17-tetraenoyl-CoA + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = (5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenoyl-CoA + 2 ferricytochrome b₅ + 2 H₂O

Other name(s):

FADS1 (gene name); acyl-CoA 5-desaturase (methylene-interrupted)

Systematic name:

Δ⁸-acyl-CoA,ferrocytochrome b₅:oxygen oxidoreductase (5,6-cis-dehydrogenating)

Comments:

The enzyme introduces a cis double bond at carbon 5 of acyl-CoAs that contain a double bond at position 8. The enzymes from algae, mosses, mammals and the protozoan Leishmania major catalyse the desaturation of dihomo-γ-linoleate [(8Z,11Z,14Z)-icosa-8,11,14-trienoate] and (8Z,11Z,14Z,17Z)-icosa-8,11,14,17-tetraenoate to generate arachidonate and (5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenoate, respectively. The enzyme contains a cytochrome b₅ domain that acts as the direct electron donor to the desaturase active site and does not require an external cytochrome. cf. EC 1.14.19.37, acyl-CoA 5-desaturase.

Links to other databases:

References:

1.	Cho, H.P., Nakamura, M. and Clarke, S.D. Cloning, expression, and fatty acid regulation of the human Δ⁵ desaturase. J. Biol. Chem. 274 (1999) 37335–37339. [DOI] [PMID: 10601301]
2.	Leonard, A.E., Kelder, B., Bobik, E.G., Chuang, L.T., Parker-Barnes, J.M., Thurmond, J.M., Kroeger, P.E., Kopchick, J.J., Huang, Y.S. and Mukerji, P. cDNA cloning and characterization of human Δ⁵-desaturase involved in the biosynthesis of arachidonic acid. Biochem. J. 347 Pt 3 (2000) 719–724. [PMID: 10769175]
3.	Tripodi, K.E., Buttigliero, L.V., Altabe, S.G. and Uttaro, A.D. Functional characterization of front-end desaturases from trypanosomatids depicts the first polyunsaturated fatty acid biosynthetic pathway from a parasitic protozoan. FEBS J. 273 (2006) 271–280. [DOI] [PMID: 16403015]
4.	Tavares, S., Grotkjær, T., Obsen, T., Haslam, R.P., Napier, J.A. and Gunnarsson, N. Metabolic engineering of Saccharomyces cerevisiae for production of eicosapentaenoic acid, using a novel Δ⁵-desaturase from Paramecium tetraurelia. Appl. Environ. Microbiol. 77 (2011) 1854–1861. [DOI] [PMID: 21193673]

[EC 1.14.19.44 created 2015]

1.14.19.45

Accepted name:

sn-1 oleoyl-lipid 12-desaturase

Reaction:

a 1-oleoyl-2-acyl-[glycerolipid] + 2 reduced ferredoxin [iron-sulfur] cluster + O₂ + 2 H⁺ = a 1-linoleoyl-2-acyl-[glycerolipid] + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H₂O

Other name(s):

desA (gene name)

Systematic name:

1-oleoyl-2-acyl-[glycerolipid],ferredoxin:oxygen oxidoreductase (12,13-cis-dehydrogenating)

Comments:

The enzyme, characterized from cyanobacteria, introduces a cis double bond at carbon 12 of oleoyl groups (18:1) attached to the sn-1 position of glycerolipids. The enzyme is a methyl-end desaturase, introducing the new double bond between a pre-existing double bond and the methyl-end of the fatty acid. It is nonspecific with respect to the polar head group of the glycerolipid.

Links to other databases:

References:

1.	Wada, H., Gombos, Z. and Murata, N. Enhancement of chilling tolerance of a cyanobacterium by genetic manipulation of fatty acid desaturation. Nature 347 (1990) 200–203. [DOI] [PMID: 2118597]
2.	Higashi, S. and Murata, N. An in vivo study of substrate specificities of acyl-lipid desaturases and acyltransferases in lipid synthesis in Synechocystis PCC6803. Plant Physiol. 102 (1993) 1275–1278. [PMID: 12231903]
3.	Amiri, R.M., Yur'eva, N.O., Shimshilashvili, K.R., Goldenkova-Pavlova, I.V., Pchelkin, V.P., Kuznitsova, E.I., Tsydendambaev, V.D., Trunova, T.I., Los, D.A., Jouzani, G.S. and Nosov, A.M. Expression of acyl-lipid Δ¹²-desaturase gene in prokaryotic and eukaryotic cells and its effect on cold stress tolerance of potato. J. Integr. Plant Biol. 52 (2010) 289–297. [DOI] [PMID: 20377689]

[EC 1.14.19.45 created 2015]

1.14.19.46

Accepted name:

sn-1 linoleoyl-lipid 6-desaturase

Reaction:

a 1-linoleoyl-2-acyl-[glycerolipid] + 2 reduced ferredoxin [iron-sulfur] cluster + O₂ + 2 H⁺ = a 1-γ-linolenoyl-2-acyl-[glycerolipid] + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H₂O

Other name(s):

desD (gene name)

Systematic name:

1-linoleoyl-2-acyl-[glycerolipid],ferredoxin:oxygen oxidoreductase (6,7-cis-dehydrogenating)

Comments:

The enzyme, characterized from cyanobacteria, introduces a cis double bond at carbon 6 of linoleoyl groups (18:2) attached to the sn-1 position of glycerolipids. The enzyme is a front-end desaturase, introducing the new double bond between a pre-existing double bond and the carboxyl-end of the fatty acid. It is nonspecific with respect to the polar head group of the glycerolipid.

Links to other databases:

References:

1.	Higashi, S. and Murata, N. An in vivo study of substrate specificities of acyl-lipid desaturases and acyltransferases in lipid synthesis in Synechocystis PCC6803. Plant Physiol. 102 (1993) 1275–1278. [PMID: 12231903]
2.	Reddy, A.S. and Thomas, T.L. Expression of a cyanobacterial Δ⁶-desaturase gene results in γ-linolenic acid production in transgenic plants. Nat. Biotechnol. 14 (1996) 639–642. [DOI] [PMID: 9630958]
3.	Kurdrid, P., Subudhi, S., Hongsthong, A., Ruengjitchatchawalya, M. and Tanticharoen, M. Functional expression of Spirulina-Δ⁶ desaturase gene in yeast, Saccharomyces cerevisiae. Mol. Biol. Rep. 32 (2005) 215–226. [DOI] [PMID: 16328883]

[EC 1.14.19.46 created 2015]

1.14.19.47

Accepted name:

acyl-lipid (9-3)-desaturase

Reaction:

(1) an α-linolenoyl-[glycerolipid] + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = a stearidonoyl-[glycerolipid] + 2 ferricytochrome b₅ + 2 H₂O
(2) a linoleoyl-[glycerolipid] + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = a γ-linolenoyl-[glycerolipid] + 2 ferricytochrome b₅ + 2 H₂O

Glossary:

stearidonic acid = (6Z,9Z,12Z,15Z)-octadeca-6,9,12,15-tetraenoic acid

Other name(s):

DES6 (gene name); acyl-lipid 6-desaturase; acyl-lipid Δ⁶-desaturase; Δ⁶-desaturase (ambiguous)

Systematic name:

Δ⁹ acyl-[glycerolipid],ferrocytochrome b₅:oxygen oxidoreductase (6,7-cis-dehydrogenating)

Comments:

The enzyme, characterized from the moss Physcomitrella patens and the plant Borago officinalis (borage), introduces a cis double bond at carbon 6 of several acyl-lipids that contain an existing Δ⁹ cis double bond. The enzyme contains a cytochrome b₅ domain that acts as the electron donor for the active site of the desaturase.

Links to other databases:

References:

1.	Sayanova, O., Smith, M.A., Lapinskas, P., Stobart, A.K., Dobson, G., Christie, W.W., Shewry, P.R. and Napier, J.A. Expression of a borage desaturase cDNA containing an N-terminal cytochrome b₅ domain results in the accumulation of high levels of Δ⁶-desaturated fatty acids in transgenic tobacco. Proc. Natl. Acad. Sci. USA 94 (1997) 4211–4216. [DOI] [PMID: 9108131]
2.	Girke, T., Schmidt, H., Zähringer, U., Reski, R. and Heinz, E. Identification of a novel Δ⁶-acyl-group desaturase by targeted gene disruption in Physcomitrella patens. Plant J. 15 (1998) 39–48. [DOI] [PMID: 9744093]

[EC 1.14.19.47 created 2015]

1.14.99.3

Transferred entry:

heme oxygenase (biliverdin-producing). Now EC 1.14.14.18, heme oxygenase (biliverdin-producing)

[EC 1.14.99.3 created 1972, modified 2006, deleted 2015]

1.14.99.9

Transferred entry:

steroid 17α-monooxygenase, now classified as EC 1.14.14.19, steroid 17α-monooxygenase

[EC 1.14.99.9 created 1961 as EC 1.99.1.9, transferred 1965 to EC 1.14.1.7, transferred 1972 to EC 1.14.99.9, modified 2013, deleted 2015]

1.14.99.10

Transferred entry:

steroid 21-monooxygenase. Now EC 1.14.14.16, steroid 21-monooxygenase

[EC 1.14.99.10 created 1961 as EC 1.99.1.11, transferred 1965 to EC 1.14.1.8, transferred 1972 to EC 1.14.99.10, modified 2013, deleted 2015]

1.14.99.33

Transferred entry:

Δ¹²-fatty acid dehydrogenase. Now EC 1.14.19.39, acyl-lipid Δ¹²-acetylenase

[EC 1.14.99.33 created 2000, deleted 2015]

1.14.99.36

Transferred entry:

β-carotene 15,15-monooxygenase. Now classified as EC 1.13.11.63, β-carotene 15,15′-dioxygenase.

[EC 1.14.99.36 created 1972 as EC 1.13.11.21, transferred 2001 to EC 1.14.99.36, deleted 2015]

1.21.99.4

Accepted name:

thyroxine 5′-deiodinase

Reaction:

3,3′,5-triiodo-L-thyronine + iodide + acceptor + H⁺ = L-thyroxine + reduced acceptor

Glossary:

3,3′,5-triiodo-L-thyronine = O-(4-hydroxy-3-iodophenyl)-3,5-diiodo-L-tyrosine
L-thyroxine = O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-L-tyrosine

Other name(s):

diiodothyronine 5′-deiodinase [ambiguous]; iodothyronine 5′-deiodinase; iodothyronine outer ring monodeiodinase; type I iodothyronine deiodinase; type II iodothyronine deiodinase; thyroxine 5-deiodinase [misleading]; L-thyroxine iodohydrolase (reducing)

Systematic name:

3,3′,5-triiodo-L-thyronine,iodide:acceptor oxidoreductase (iodinating)

Comments:

The enzyme activity has only been demonstrated in the direction of 5′-deiodination, which renders the thyroid hormone more active. The enzyme consists of type I and type II enzymes, both containing selenocysteine, but with different kinetics. For the type I enzyme the first reaction is a reductive deiodination converting the -Se-H group of the enzyme into an -Se-I group; the reductant then reconverts this into -Se-H, releasing iodide.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 70712-46-8

References:

1.	Chopra, I.J. and Teco, G.N.C. Characteristics of inner ring (3 or 5) monodeiodination of 3,5-diiodothyronine in rat liver: evidence suggesting marked similarities of inner and outer ring deiodinases for iodothyronines. Endocrinology 110 (1982) 89–97. [DOI] [PMID: 7053997]
2.	Goswani, A., Leonard, J.L. and Rosenberg, I.N. Inhibition by coumadin anticoagulants of enzymatic outer ring monodeiodination of iodothyronines. Biochem. Biophys. Res. Commun. 104 (1982) 1231–1238. [DOI] [PMID: 6176242]
3.	Smallridge, R.C., Burman, K.D., Ward, K.E., Wartofsky, L., Dimond, R.C., Wright, F.D. and Lathan, K.R. 3′,5′-Diiodothyronine to 3′-monoiodothyronine conversion in the fed and fasted rat: enzyme characteristics and evidence for two distinct 5′-deiodinases. Endocrinology 108 (1981) 2336–2345. [DOI] [PMID: 7227308]
4.	Körhle, J. Iodothyronine deiodinases. Methods Enzymol. 347 (2002) 125–167. [PMID: 11898402]

[EC 1.21.99.4 created 1984 as EC 3.8.1.4, transferred 2003 to EC 1.97.1.10, transferred 2015 to EC 1.21.99.4]

1.97.1.10

Transferred entry:

thyroxine 5′-deiodinase. Now EC 1.21.99.4 thyroxine 5′-deiodinase

[EC 1.97.1.10 created 1984 as EC 3.8.1.4, transferred 2003 to EC 1.97.1.10, deleted 2015]

2.1.1.124

Deleted entry:

[cytochrome c]-arginine N-methyltransferase. Now covered by EC 2.1.1.319, type I protein arginine methyltransferase, EC 2.1.1.320, type II protein arginine methyltransferase, EC 2.1.1.321, type III protein arginine methyltransferase and EC 2.1.1.322, type IV protein arginine methyltransferase

[EC 2.1.1.124 created 1999 (EC 2.1.1.23 created 1972, modified 1976, modified 1983, part incorporated 1999), deleted 2015]

2.1.1.125

Deleted entry:

histone-arginine N-methyltransferase. Now covered by EC 2.1.1.319, type I protein arginine methyltransferase, EC 2.1.1.320, type II protein arginine methyltransferase, EC 2.1.1.321, type III protein arginine methyltransferase and EC 2.1.1.322, type IV protein arginine methyltransferase

[EC 2.1.1.125 created 1999 (EC 2.1.1.23 created 1972, modified 1976, modified 1983, part incorporated 1999), deleted 2015]

2.1.1.126

Deleted entry:

[myelin basic protein]-arginine N-methyltransferase. Now covered by EC 2.1.1.319, type I protein arginine methyltransferase, EC 2.1.1.320, type II protein arginine methyltransferase, EC 2.1.1.321, type III protein arginine methyltransferase and EC 2.1.1.322, type IV protein arginine methyltransferase

[EC 2.1.1.126 created 1999 (EC 2.1.1.23 created 1972, modified 1976, modified 1983, part incorporated 1999), deleted 2015]

2.1.1.319

Accepted name:

type I protein arginine methyltransferase

Reaction:

2 S-adenosyl-L-methionine + [protein]-L-arginine = 2 S-adenosyl-L-homocysteine + [protein]-N^ω,N^ω-dimethyl-L-arginine (overall reaction)
(1a) S-adenosyl-L-methionine + [protein]-L-arginine = S-adenosyl-L-homocysteine + [protein]-N^ω-methyl-L-arginine
(1b) S-adenosyl-L-methionine + [protein]-N^ω-methyl-L-arginine = S-adenosyl-L-homocysteine + [protein]-N^ω,N^ω-dimethyl-L-arginine

Other name(s):

PRMT1 (gene name); PRMT2 (gene name); PRMT3 (gene name); PRMT4 (gene name); PRMT6 (gene name); PRMT8 (gene name); RMT1 (gene name); CARM1 (gene name)

Systematic name:

S-adenosyl-L-methionine:[protein]-L-arginine N-methyltransferase ([protein]-N^ω,N^ω-dimethyl-L-arginine-forming)

Comments:

This eukaryotic enzyme catalyses the sequential dimethylation of one of the terminal guanidino nitrogen atoms in arginine residues, resulting in formation of asymmetric dimethylarginine residues. Some forms (e.g. PRMT1) have a very wide substrate specificity, while others (e.g. PRMT4 and PRMT6) are rather specific. The enzyme has a preference for methylating arginine residues that are flanked by one or more glycine residues [1]. PRMT1 is responsible for the bulk (about 85%) of total protein arginine methylation activity in mammalian cells [2]. cf. EC 2.1.1.320, type II protein arginine methyltransferase, EC 2.1.1.321, type III protein arginine methyltransferase, and EC 2.1.1.322, type IV protein arginine methyltransferase.

Links to other databases:

References:

1.	Gary, J.D. and Clarke, S. RNA and protein interactions modulated by protein arginine methylation. Prog. Nucleic Acid Res. Mol. Biol. 61 (1998) 65–131. [PMID: 9752719]
2.	Tang, J., Gary, J.D., Clarke, S. and Herschman, H.R. PRMT 3, a type I protein arginine N-methyltransferase that differs from PRMT1 in its oligomerization, subcellular localization, substrate specificity, and regulation. J. Biol. Chem. 273 (1998) 16935–16945. [DOI] [PMID: 9642256]
3.	Tang, J., Frankel, A., Cook, R.J., Kim, S., Paik, W.K., Williams, K.R., Clarke, S. and Herschman, H.R. PRMT1 is the predominant type I protein arginine methyltransferase in mammalian cells. J. Biol. Chem. 275 (2000) 7723–7730. [DOI] [PMID: 10713084]
4.	Frankel, A., Yadav, N., Lee, J., Branscombe, T.L., Clarke, S. and Bedford, M.T. The novel human protein arginine N-methyltransferase PRMT6 is a nuclear enzyme displaying unique substrate specificity. J. Biol. Chem. 277 (2002) 3537–3543. [DOI] [PMID: 11724789]

[EC 2.1.1.319 created 2015]

2.1.1.320

Accepted name:

type II protein arginine methyltransferase

Reaction:

2 S-adenosyl-L-methionine + [protein]-L-arginine = 2 S-adenosyl-L-homocysteine + [protein]-N^ω,N^ω′-dimethyl-L-arginine (overall reaction)
(1a) S-adenosyl-L-methionine + [protein]-L-arginine = S-adenosyl-L-homocysteine + [protein]-N^ω-methyl-L-arginine
(1b) S-adenosyl-L-methionine + [protein]-N^ω-methyl-L-arginine = S-adenosyl-L-homocysteine + [protein]-N^ω,N^ω′-dimethyl-L-arginine

Other name(s):

PRMT5 (gene name); PRMT9 (gene name)

Systematic name:

S-adenosyl-L-methionine:[protein]-L-arginine N-methyltransferase ([protein]-N^ω,N^ω′-dimethyl-L-arginine-forming)

Comments:

The enzyme catalyses the methylation of one of the terminal guanidino nitrogen atoms in arginine residues within proteins, forming monomethylarginine, followed by the methylation of the second terminal nitrogen atom to form a symmetrical dimethylarginine. The mammalian enzyme is active in both the nucleus and the cytoplasm, and plays a role in the assembly of snRNP core particles by methylating certain small nuclear ribonucleoproteins. cf. EC 2.1.1.319, type I protein arginine methyltransferase, EC 2.1.1.321, type III protein arginine methyltransferase, and EC 2.1.1.322, type IV protein arginine methyltransferase.

Links to other databases:

References:

1.	Branscombe, T.L., Frankel, A., Lee, J.H., Cook, J.R., Yang, Z., Pestka, S. and Clarke, S. PRMT5 (Janus kinase-binding protein 1) catalyzes the formation of symmetric dimethylarginine residues in proteins. J. Biol. Chem. 276 (2001) 32971–32976. [DOI] [PMID: 11413150]
2.	Wang, X., Zhang, Y., Ma, Q., Zhang, Z., Xue, Y., Bao, S. and Chong, K. SKB1-mediated symmetric dimethylation of histone H4R3 controls flowering time in Arabidopsis. EMBO J. 26 (2007) 1934–1941. [DOI] [PMID: 17363895]
3.	Lacroix, M., El Messaoudi, S., Rodier, G., Le Cam, A., Sardet, C. and Fabbrizio, E. The histone-binding protein COPR5 is required for nuclear functions of the protein arginine methyltransferase PRMT5. EMBO Rep. 9 (2008) 452–458. [DOI] [PMID: 18404153]
4.	Chari, A., Golas, M.M., Klingenhager, M., Neuenkirchen, N., Sander, B., Englbrecht, C., Sickmann, A., Stark, H. and Fischer, U. An assembly chaperone collaborates with the SMN complex to generate spliceosomal SnRNPs. Cell 135 (2008) 497–509. [DOI] [PMID: 18984161]
5.	Antonysamy, S., Bonday, Z., Campbell, R.M., Doyle, B., Druzina, Z., Gheyi, T., Han, B., Jungheim, L.N., Qian, Y., Rauch, C., Russell, M., Sauder, J.M., Wasserman, S.R., Weichert, K., Willard, F.S., Zhang, A. and Emtage, S. Crystal structure of the human PRMT5:MEP50 complex. Proc. Natl. Acad. Sci. USA 109 (2012) 17960–17965. [DOI] [PMID: 23071334]
6.	Hadjikyriacou, A., Yang, Y., Espejo, A., Bedford, M.T. and Clarke, S.G. Unique features of human protein arginine methyltransferase 9 (PRMT9) and its substrate RNA splicing factor SF3B2. J. Biol. Chem. 290 (2015) 16723–16743. [DOI] [PMID: 25979344]

[EC 2.1.1.320 created 2015]

2.1.1.321

Accepted name:

type III protein arginine methyltransferase

Reaction:

S-adenosyl-L-methionine + [protein]-L-arginine = S-adenosyl-L-homocysteine + [protein]-N^ω-methyl-L-arginine

Other name(s):

PRMT7 (gene name)

Systematic name:

S-adenosyl-L-methionine:[protein]-L-arginine N-methyltransferase ([protein]-N^ω-methyl-L-arginine-forming)

Comments:

Type III protein arginine methyltransferases catalyse the single methylation of one of the terminal nitrogen atoms of the guanidino group in an L-arginine residue within a protein. Unlike type I and type II protein arginine methyltransferases, which also catalyse this reaction, type III enzymes do not methylate the substrate any further. cf. EC 2.1.1.319, type I protein arginine methyltransferase, EC 2.1.1.320, type II protein arginine methyltransferase, and EC 2.1.1.322, type IV protein arginine methyltransferase.

Links to other databases:

References:

1.	Miranda, T.B., Miranda, M., Frankel, A. and Clarke, S. PRMT7 is a member of the protein arginine methyltransferase family with a distinct substrate specificity. J. Biol. Chem. 279 (2004) 22902–22907. [DOI] [PMID: 15044439]
2.	Gonsalvez, G.B., Tian, L., Ospina, J.K., Boisvert, F.M., Lamond, A.I. and Matera, A.G. Two distinct arginine methyltransferases are required for biogenesis of Sm-class ribonucleoproteins. J. Cell Biol. 178 (2007) 733–740. [DOI] [PMID: 17709427]
3.	Feng, Y., Hadjikyriacou, A. and Clarke, S.G. Substrate specificity of human protein arginine methyltransferase 7 (PRMT7): the importance of acidic residues in the double E loop. J. Biol. Chem. 289 (2014) 32604–32616. [DOI] [PMID: 25294873]

[EC 2.1.1.321 created 2015]

2.1.1.322

Accepted name:

type IV protein arginine methyltransferase

Reaction:

S-adenosyl-L-methionine + [protein]-L-arginine = S-adenosyl-L-homocysteine + [protein]-N⁵-methyl-L-arginine

Other name(s):

RMT2 (gene name)

Systematic name:

S-adenosyl-L-methionine:[protein]-L-arginine N-methyltransferase ([protein]-N⁵-methyl-L-arginine-forming)

Comments:

This enzyme, characterized from the yeast Saccharomyces cerevisiae, methylates the the δ-nitrogen atom of arginine residues within proteins. Among its substrates are Arg⁶⁷ of the ribosomal protein L12. cf. EC 2.1.1.319, type I protein arginine methyltransferase, EC 2.1.1.320, type II protein arginine methyltransferase, and EC 2.1.1.321, type III protein arginine methyltransferase.

Links to other databases:

References:

1.	Niewmierzycka, A. and Clarke, S. S-Adenosylmethionine-dependent methylation in Saccharomyces cerevisiae. Identification of a novel protein arginine methyltransferase. J. Biol. Chem. 274 (1999) 814–824. [DOI] [PMID: 9873020]
2.	Chern, M.K., Chang, K.N., Liu, L.F., Tam, T.C., Liu, Y.C., Liang, Y.L. and Tam, M.F. Yeast ribosomal protein L12 is a substrate of protein-arginine methyltransferase 2. J. Biol. Chem. 277 (2002) 15345–15353. [DOI] [PMID: 11856739]
3.	Olsson, I., Berrez, J.M., Leipus, A., Ostlund, C. and Mutvei, A. The arginine methyltransferase Rmt2 is enriched in the nucleus and co-purifies with the nuclear porins Nup49, Nup57 and Nup100. Exp. Cell Res. 313 (2007) 1778–1789. [DOI] [PMID: 17448464]

[EC 2.1.1.322 created 2015]

*EC

2.3.1.60

Accepted name:

gentamicin 3-N-acetyltransferase

Reaction:

acetyl-CoA + gentamicin C = CoA + N³-acetylgentamicin C

Other name(s):

gentamycin acetyltransferase I; aminoglycoside acetyltransferase AAC(3)-1; gentamycin 3-N-acetyltransferase; acetyl-CoA:gentamycin-C N³-acetyltransferase; acetyl-CoA:gentamicin-C N^3′-acetyltransferase (incorrect); gentamicin 3′-N-acetyltransferase (incorrect)

Systematic name:

acetyl-CoA:gentamicin-C N³-acetyltransferase

Comments:

Also acetylates sisomicin.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 58500-58-6

References:

1.	Angelatou, F., Litsas, S.B. and Kontomichalou, P. Purification and properties of two gentamicin-modifying enzymes, coded by a single plasmid pPK237 originating from Pseudomonas aeruginosa. J. Antibiot. 35 (1982) 235–244. [PMID: 6281224]
2.	Biddlecome, S., Haas, J., Davies, G.H., Miller, D., Rane, F. and Daniels, P.J.L. Enzymatic modification of aminoglycoside antibiotics: a new 3-N-acetylating enzyme from a Pseudomonas aeruginosa isolate. Antimicrob. Agents Chemother. 9 (1976) 951–955. [PMID: 820250]
3.	Williams, J.W. and Northrop, D.B. Purification and properties of gentamicin acetyltransferase I. Biochemistry 15 (1976) 125–131. [PMID: 764855]

[EC 2.3.1.60 created 1976, modified 2015]

*EC

2.3.1.81

Accepted name:

aminoglycoside 3-N-acetyltransferase

Reaction:

acetyl-CoA + a 2-deoxystreptamine antibiotic = CoA + N³-acetyl-2-deoxystreptamine antibiotic

For diagram of neamine and ribostamycin biosynthesis, click here

Glossary:

kanamycin

Other name(s):

3-aminoglycoside acetyltransferase; 3-N-aminoglycoside acetyltransferase; aminoglycoside N³-acetyltransferase; acetyl-CoA:2-deoxystreptamine-antibiotic N^3′-acetyltransferase (incorrect); aminoglycoside N^3′-acetyltransferase (incorrect)

Systematic name:

acetyl-CoA:2-deoxystreptamine-antibiotic N³-acetyltransferase

Comments:

Different from EC 2.3.1.60 gentamicin 3-N-acetyltransferase. A wide range of antibiotics containing the 2-deoxystreptamine ring can act as acceptors, including gentamicin, kanamycin, tobramycin, neomycin and apramycin.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 60120-42-5

References:

1.	Davies, J. and O'Connor, S. Enzymatic modification of aminoglycoside antibiotics: 3-N-Acetyltransferase with broad specificity that determines resistance to the novel aminoglycoside apramycin. Antimicrob. Agents Chemother. 14 (1978) 69–72. [PMID: 356726]

[EC 2.3.1.81 created 1984, modified 2015]

2.3.1.154

Transferred entry:

Propionyl-CoA C²-trimethyltridecanoyltransferase. Now EC 2.3.1.176, propanoyl-CoA C-acyltransferase.

[EC 2.3.1.154 created 2000, deleted 2015]

2.3.1.251

Accepted name:

lipid IV_A palmitoyltransferase

Reaction:

(1) 1-palmitoyl-2-acyl-sn-glycero-3-phosphocholine + hexa-acyl lipid A = 2-acyl-sn-glycero-3-phosphocholine + hepta-acyl lipid A
(2) 1-palmitoyl-2-acyl-sn-glycero-3-phosphocholine + lipid II_A = 2-acyl-sn-glycero-3-phosphocholine + lipid II_B
(3) 1-palmitoyl-2-acyl-sn-glycero-3-phosphocholine + lipid IV_A = 2-acyl-sn-glycero-3-phosphocholine + lipid IV_B

For diagram of lipid IV_B biosynthesis, click here

Glossary:

palmitoyl = hexadecanoyl
hexa-acyl lipid A = 2-deoxy-2-[(3R)-3-(tetradecanoyloxy)tetradecanamido]-3-O-[(3R)-3-(dodecanoyloxy)tetradecanoyl]-4-O-phospho-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxytetradecanoyl]-2-[(3R)-3-hydroxytetradecanamido]-α-D-glucopyranosyl phosphate
hepta-acyl lipid A = 2-deoxy-2-[(3R)-3-(tetradecanoyloxy)tetradecanamido]-3-O-[(3R)-3-(dodecanoyloxy)tetradecanoyl]-4-O-phospho-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxytetradecanoyl]-2-[(3R)-3-(hexadecanoyloxy)tetradecanamido]-α-D-glucopyranosyl phosphate
lipid II_A = 4-amino-4-deoxy-β-L-arabinopyranosyl 2-deoxy-2-[(3R)-3-hydroxytetradecanamido]-3-O-[(3R)-3-hydroxytetradecanoyl]-4-O-phospho-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxytetradecanoyl]-2-[(3R)-3-hydroxytetradecanamido]-α-D-glucopyranose phosphate
lipid II_B = 4-amino-4-deoxy-β-L-arabinopyranosyl 2-deoxy-2-[(3R)-3-hydroxytetradecanamido]-3-O-[(3R)-3-hydroxytetradecanoyl]-4-O-phospho-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxytetradecanoyl]-2-[(3R)-3-(hexadecanoyloxy)tetradecanamido]-α-D-glucopyranosyl phosphate
lipid IV_A = 2-deoxy-2-[(3R)-3-hydroxytetradecanamido]-3-O-[(3R)-3-hydroxytetradecanoyl]-4-O-phospho-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxytetradecanoyl]-2-[(3R)-3-hydroxytetradecanamido]-α-D-glucopyranose phosphate
lipid IV_B = 2-deoxy-2-[(3R)-3-hydroxytetradecanamido]-3-O-[(3R)-3-hydroxytetradecanoyl]-4-O-phospho-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxytetradecanoyl]-2-[(3R)-3-(hexadecanoyloxy)tetradecanamido]-α-D-glucopyranosyl phosphate

Other name(s):

PagP; crcA (gene name)

Systematic name:

1-palmitoyl-2-acyl-sn-glycero-3-phosphocholine:lipid-IV_A palmitoyltransferase

Comments:

Isolated from the bacteria Escherichia coli and Salmonella typhimurium. The enzyme prefers phosphatidylcholine with a palmitoyl group at the sn-1 position and palmitoyl or stearoyl groups at the sn-2 position. There is some activity with corresponding phosphatidylserines but only weak activity with other diacylphosphatidyl compounds. The enzyme also acts on Kdo-(2→4)-Kdo-(2→6)-lipid IV_A.

Links to other databases:

References:

1.	Bishop, R.E., Gibbons, H.S., Guina, T., Trent, M.S., Miller, S.I. and Raetz, C.R. Transfer of palmitate from phospholipids to lipid A in outer membranes of gram-negative bacteria. EMBO J. 19 (2000) 5071–5080. [DOI] [PMID: 11013210]
2.	Cuesta-Seijo, J.A., Neale, C., Khan, M.A., Moktar, J., Tran, C.D., Bishop, R.E., Pomes, R. and Prive, G.G. PagP crystallized from SDS/cosolvent reveals the route for phospholipid access to the hydrocarbon ruler. Structure 18 (2010) 1210–1219. [DOI] [PMID: 20826347]

[EC 2.3.1.251 created 2015]

2.4.1.157

Transferred entry:

1,2-diacylglycerol 3-glucosyltransferase. Now classified as EC 2.4.1.336, monoglucosyldiacylglycerol synthase, and EC 2.4.1.337, 1,2-diacylglycerol 3-α-glucosyltransferase

[EC 2.4.1.157 created 1986, deleted 2015]

*EC

2.4.1.326

Accepted name:

aklavinone 7-L-rhodosaminyltransferase

Reaction:

dTDP-β-L-rhodosamine + aklavinone = dTDP + aclacinomycin T

For diagram of aklavinone biosynthesis, click here

Glossary:

dTDP-β-L-rhodosamine = dTDP-2,3,6-trideoxy-3-dimethylamino-β-L-lyxo-hexose
aklavinone = methyl (1R,2R,4S)-2-ethyl-2,4,5,7-tetrahydroxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracene-1-carboxylate
aclacinomycin T = 7-O-(α-L-rhodosaminyl)aklavinone

Other name(s):

AknS/AknT; aklavinone 7-β-L-rhodosaminyltransferase; dTDP-β-L-rhodosamine:aklavinone 7-α-L-rhodosaminyltransferase

Systematic name:

dTDP-β-L-rhodosamine:aklavinone 7-α-L-rhodosaminyltransferase (configuration-inverting)

Comments:

Isolated from the bacterium Streptomyces galilaeus. Forms a complex with its accessory protein AknT, and has very low activity in its absence. The enzyme can also use dTDP-2-deoxy-β-L-fucose. Involved in the biosynthesis of other aclacinomycins.

Links to other databases:

References:

1.	Lu, W., Leimkuhler, C., Gatto, G.J., Jr., Kruger, R.G., Oberthur, M., Kahne, D. and Walsh, C.T. AknT is an activating protein for the glycosyltransferase AknS in L-aminodeoxysugar transfer to the aglycone of aclacinomycin A. Chem. Biol. 12 (2005) 527–534. [DOI] [PMID: 15911373]
2.	Leimkuhler, C., Fridman, M., Lupoli, T., Walker, S., Walsh, C.T. and Kahne, D. Characterization of rhodosaminyl transfer by the AknS/AknT glycosylation complex and its use in reconstituting the biosynthetic pathway of aclacinomycin A. J. Am. Chem. Soc. 129 (2007) 10546–10550. [DOI] [PMID: 17685523]

[EC 2.4.1.326 created 2014, modified 2015]

2.4.1.335

Accepted name:

dolichyl N-acetyl-α-D-glucosaminyl phosphate 3-β-D-2,3-diacetamido-2,3-dideoxy-β-D-glucuronosyltransferase

Reaction:

UDP-2,3-diacetamido-2,3-dideoxy-α-D-glucuronate + an archaeal dolichyl N-acetyl-α-D-glucosaminyl phosphate = UDP + an archaeal dolichyl 3-O-(2,3-diacetamido-2,3-dideoxy-β-D-glucuronsyl)-N-acetyl-α-D-glucosaminyl phosphate

Other name(s):

AglC; UDP-Glc-2,3-diNAcA glycosyltransferase

Systematic name:

UDP-2,3-diacetamido-2,3-dideoxy-α-D-glucuronate:dolichyl N-acetyl-α-D-glucosaminyl-phosphate 3-β-D-2,3-diacetamido-2,3-dideoxy-β-D-glucuronosyltransferase

Comments:

The enzyme, characterized from the methanogenic archaeon Methanococcus voltae, participates in the N-glycosylation of proteins. Dolichol used by archaea is different from that used by eukaryotes. It is much shorter (C₅₅-C₆₀), it is α,ω-saturated and it may have additional unsaturated positions in the chain.

Links to other databases:

References:

1.	Larkin, A., Chang, M.M., Whitworth, G.E. and Imperiali, B. Biochemical evidence for an alternate pathway in N-linked glycoprotein biosynthesis. Nat. Chem. Biol. 9 (2013) 367–373. [DOI] [PMID: 23624439]

[EC 2.4.1.335 created 2015]

2.4.1.336

Accepted name:

monoglucosyldiacylglycerol synthase

Reaction:

UDP-α-D-glucose + a 1,2-diacyl-sn-glycerol = UDP + a 1,2-diacyl-3-O-(β-D-glucopyranosyl)-sn-glycerol

Glossary:

a 1,2-diacyl-3-O-(β-D-glucopyranosyl)-sn-glycerol = a β-monoglucosyldiacylglycerol = a GlcDG

Other name(s):

mgdA (gene name)

Systematic name:

UDP-α-D-glucose:1,2-diacyl-sn-glycerol 3-β-D-glucosyltransferase

Comments:

The enzymes from cyanobacteria are involved in the biosynthesis of galactolipids found in their photosynthetic membranes. The enzyme belongs to the GT2 family of configuration-inverting glycosyltranferases [2]. cf. EC 2.4.1.337, 1,2-diacylglycerol 3-α-glucosyltransferase.

Links to other databases:

References:

1.	Sato, N. and Murata, N. Lipid biosynthesis in the blue-green-alga (cyanobacterium), Anabaena variabilis. 3. UDP-glucose-diacylglycerol glucosyltransferase activity in vitro. Plant Cell Physiol. 23 (1982) 1115–1120.
2.	Awai, K., Kakimoto, T., Awai, C., Kaneko, T., Nakamura, Y., Takamiya, K., Wada, H. and Ohta, H. Comparative genomic analysis revealed a gene for monoglucosyldiacylglycerol synthase, an enzyme for photosynthetic membrane lipid synthesis in cyanobacteria. Plant Physiol. 141 (2006) 1120–1127. [DOI] [PMID: 16714404]
3.	Yuzawa, Y., Shimojima, M., Sato, R., Mizusawa, N., Ikeda, K., Suzuki, M., Iwai, M., Hori, K., Wada, H., Masuda, S. and Ohta, H. Cyanobacterial monogalactosyldiacylglycerol-synthesis pathway is involved in normal unsaturation of galactolipids and low-temperature adaptation of Synechocystis sp. PCC 6803. Biochim. Biophys. Acta 1841 (2014) 475–483. [DOI] [PMID: 24370445]

[EC 2.4.1.336 created 2015]

2.4.1.337

Accepted name:

1,2-diacylglycerol 3-α-glucosyltransferase

Reaction:

UDP-α-D-glucose + a 1,2-diacyl-sn-glycerol = UDP + a 1,2-diacyl-3-O-(α-D-glucopyranosyl)-sn-glycerol

Other name(s):

mgs (gene name); UDP-glucose:diacylglycerol glucosyltransferase; UDP-glucose:1,2-diacylglycerol glucosyltransferase; uridine diphosphoglucose-diacylglycerol glucosyltransferase; UDP-glucose-diacylglycerol glucosyltransferase; UDP-glucose:1,2-diacylglycerol 3-D-glucosyltransferase; UDP-glucose:1,2-diacyl-sn-glycerol 3-D-glucosyltransferase; 1,2-diacylglycerol 3-glucosyltransferase (ambiguous)

Systematic name:

UDP-α-D-glucose:1,2-diacyl-sn-glycerol 3-α-D-glucosyltransferase

Comments:

The enzyme from the bacterium Acholeplasma laidlawii, which lacks a cell wall, produces the major non-bilayer lipid in the organism. The enzyme from the bacterium Agrobacterium tumefaciens acts under phosphate deprivation, generating glycolipids as surrogates for phospholipids. The enzyme belongs to the GT4 family of configuration-retaining glycosyltransferases. Many diacylglycerols with long-chain acyl groups can act as acceptors. cf. EC 2.4.1.336, monoglucosyldiacylglycerol synthase.

Links to other databases:

References:

1.	Karlsson, O.P., Dahlqvist, A., Vikstrom, S. and Wieslander, A. Lipid dependence and basic kinetics of the purified 1,2-diacylglycerol 3-glucosyltransferase from membranes of Acholeplasma laidlawii. J. Biol. Chem. 272 (1997) 929–936. [DOI] [PMID: 8995384]
2.	Li, L., Storm, P., Karlsson, O.P., Berg, S. and Wieslander, A. Irreversible binding and activity control of the 1,2-diacylglycerol 3-glucosyltransferase from Acholeplasma laidlawii at an anionic lipid bilayer surface. Biochemistry 42 (2003) 9677–9686. [DOI] [PMID: 12911309]
3.	Berg, S., Edman, M., Li, L., Wikstrom, M. and Wieslander, A. Sequence properties of the 1,2-diacylglycerol 3-glucosyltransferase from Acholeplasma laidlawii membranes. Recognition of a large group of lipid glycosyltransferases in eubacteria and archaea. J. Biol. Chem. 276 (2001) 22056–22063. [DOI] [PMID: 11294844]
4.	Semeniuk, A., Sohlenkamp, C., Duda, K. and Holzl, G. A bifunctional glycosyltransferase from Agrobacterium tumefaciens synthesizes monoglucosyl and glucuronosyl diacylglycerol under phosphate deprivation. J. Biol. Chem. 289 (2014) 10104–10114. [DOI] [PMID: 24558041]

[EC 2.4.1.337 created 2015]

*EC

2.4.2.54

Accepted name:

β-ribofuranosylphenol 5′-phosphate synthase

Reaction:

5-phospho-α-D-ribose 1-diphosphate + 4-hydroxybenzoate = 4-(β-D-ribofuranosyl)phenol 5′-phosphate + CO₂ + diphosphate

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

Other name(s):

β-RFAP synthase (incorrect); β-RFA-P synthase (incorrect); AF2089 (gene name); MJ1427 (gene name); β-ribofuranosylhydroxybenzene 5′-phosphate synthase; 4-(β-D-ribofuranosyl)aminobenzene 5′-phosphate synthase (incorrect); β-ribofuranosylaminobenzene 5′-phosphate synthase (incorrect); 5-phospho-α-D-ribose 1-diphosphate:4-aminobenzoate 5-phospho-β-D-ribofuranosyltransferase (decarboxylating) (incorrect)

Systematic name:

5-phospho-α-D-ribose-1-diphosphate:4-hydroxybenzoate 5-phospho-β-D-ribofuranosyltransferase (decarboxylating)

Comments:

The enzyme is involved in biosynthesis of tetrahydromethanopterin in archaea. It can utilize both 4-hydroxybenzoate and 4-aminobenzoate as substrates, but only the former is known to be produced by methanogenic archaea [4]. The activity is dependent on Mg²⁺ or Mn²⁺ [1].

Links to other databases:

References:

1.	Rasche, M.E. and White, R.H. Mechanism for the enzymatic formation of 4-(β-D-ribofuranosyl)aminobenzene 5′-phosphate during the biosynthesis of methanopterin. Biochemistry 37 (1998) 11343–11351. [DOI] [PMID: 9698382]
2.	Scott, J.W. and Rasche, M.E. Purification, overproduction, and partial characterization of β-RFAP synthase, a key enzyme in the methanopterin biosynthesis pathway. J. Bacteriol. 184 (2002) 4442–4448. [DOI] [PMID: 12142414]
3.	Dumitru, R.V. and Ragsdale, S.W. Mechanism of 4-(β-D-ribofuranosyl)aminobenzene 5′-phosphate synthase, a key enzyme in the methanopterin biosynthetic pathway. J. Biol. Chem. 279 (2004) 39389–39395. [DOI] [PMID: 15262968]
4.	White, R.H. The conversion of a phenol to an aniline occurs in the biochemical formation of the 1-(4-aminophenyl)-1-deoxy-D-ribitol moiety in methanopterin. Biochemistry 50 (2011) 6041–6052. [DOI] [PMID: 21634403]
5.	Bechard, M.E., Farahani, P., Greene, D., Pham, A., Orry, A. and Rasche, M.E. Purification, kinetic characterization, and site-directed mutagenesis of Methanothermobacter thermautotrophicus RFAP synthase produced in Escherichia coli. AIMS Microbiol 5 (2019) 186–204. [DOI] [PMID: 31663056]

[EC 2.4.2.54 created 2013, modified 2014, modified 2015]

2.4.99.21

Accepted name:

dolichyl-phosphooligosaccharide-protein glycotransferase

Reaction:

an archaeal dolichyl phosphooligosaccharide + [protein]-L-asparagine = an archaeal dolichyl phosphate + a glycoprotein with the oligosaccharide chain attached by N-β-D-glycosyl linkage to a protein L-asparagine

Other name(s):

AglB; archaeal oligosaccharyl transferase; dolichyl-monophosphooligosaccharide-protein glycotransferase

Systematic name:

dolichyl-phosphooligosaccharide:protein-L-asparagine N-β-D-oligosaccharidotransferase

Comments:

The enzyme, characterized from the archaea Methanococcus voltae and Haloferax volcanii, transfers a glycan component from dolichyl phosphooligosaccharide to external proteins. It is different from EC 2.4.99.18, dolichyl-diphosphooligosaccharide-protein glycotransferase, which uses dolichyl diphosphate as carrier compound in bacteria and eukaryotes. The enzyme participates in the N-glycosylation of proteins in some archaea. It requires Mn²⁺. Dolichol used by archaea is different from that used by eukaryotes. It is much shorter (C₅₅-C₆₀), it is α,ω-saturated and it may have additional unsaturated positions in the chain.

Links to other databases:

References:

1.	Chaban, B., Voisin, S., Kelly, J., Logan, S.M. and Jarrell, K.F. Identification of genes involved in the biosynthesis and attachment of Methanococcus voltae N-linked glycans: insight into N-linked glycosylation pathways in Archaea. Mol. Microbiol. 61 (2006) 259–268. [DOI] [PMID: 16824110]
2.	Larkin, A., Chang, M.M., Whitworth, G.E. and Imperiali, B. Biochemical evidence for an alternate pathway in N-linked glycoprotein biosynthesis. Nat. Chem. Biol. 9 (2013) 367–373. [DOI] [PMID: 23624439]
3.	Cohen-Rosenzweig, C., Guan, Z., Shaanan, B. and Eichler, J. Substrate promiscuity: AglB, the archaeal oligosaccharyltransferase, can process a variety of lipid-linked glycans. Appl. Environ. Microbiol. 80 (2014) 486–496. [DOI] [PMID: 24212570]

[EC 2.4.99.21 created 2015]

*EC

2.5.1.3

Accepted name:

thiamine phosphate synthase

Reaction:

(1) 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate = diphosphate + thiamine phosphate + CO₂
(2) 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2-(2-carboxy-4-methylthiazol-5-yl)ethyl phosphate = diphosphate + thiamine phosphate + CO₂
(3) 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 4-methyl-5-(2-phosphooxyethyl)thiazole = diphosphate + thiamine phosphate

For diagram of thiamine diphosphate biosynthesis, click here

Other name(s):

thiamine phosphate pyrophosphorylase; thiamine monophosphate pyrophosphorylase; TMP-PPase; thiamine-phosphate diphosphorylase; thiE (gene name); TH1 (gene name); THI6 (gene name); 2-methyl-4-amino-5-hydroxymethylpyrimidine-diphosphate:4-methyl-5-(2-phosphoethyl)thiazole 2-methyl-4-aminopyrimidine-5-methenyltransferase; 4-amino-2-methyl-5-diphosphomethylpyrimidine:2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate 4-amino-2-methylpyrimidine-5-methenyltransferase (decarboxylating)

Systematic name:

4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine:2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate 4-amino-2-methylpyrimidine-5-methenyltransferase (decarboxylating)

Comments:

The enzyme catalyses the penultimate reaction in thiamine de novo biosynthesis, condensing the pyrimidine and thiazole components. The enzyme is thought to accept the product of EC 2.8.1.10, thiazole synthase, as its substrate. However, it has been shown that in some bacteria, such as Bacillus subtilis, an additional enzyme, thiazole tautomerase (EC 5.3.99.10) converts that compound into its tautomer 2-(2-carboxy-4-methylthiazol-5-yl)ethyl phosphate, and that it is the latter that serves as the substrate for the synthase. In addition to this activity, the enzyme participates in a salvage pathway, acting on 4-methyl-5-(2-phosphooxyethyl)thiazole, which is produced from thiamine degradation products. In yeast this activity is found in a bifunctional enzyme (THI6) and in the plant Arabidopsis thaliana the activity is part of a trifunctional enzyme (TH1).

Links to other databases:

BRENDA, EXPASY, Gene, GTD, KEGG, PDB, CAS registry number: 9030-30-2

References:

1.	Camiener, G.W. and Brown, G.M. The biosynthesis of thiamine. 2. Fractionation of enzyme system and identification of thiazole monophosphate and thiamine monophosphate as intermediates. J. Biol. Chem. 235 (1960) 2411–2417. [PMID: 13807175]
2.	Leder, I.G. The enzymatic synthesis of thiamine monophosphate. J. Biol. Chem. 236 (1961) 3066–3071. [PMID: 14463407]
3.	Kawasaki, Y. Copurification of hydroxyethylthiazole kinase and thiamine-phosphate pyrophosphorylase of Saccharomyces cerevisiae: characterization of hydroxyethylthiazole kinase as a bifunctional enzyme in the thiamine biosynthetic pathway. J. Bacteriol. 175 (1993) 5153–5158. [DOI] [PMID: 8394314]
4.	Backstrom, A.D., McMordie, R.A.S. and Begley, T.P. Biosynthesis of thiamin I: the function of the thiE gene product. J. Am. Chem. Soc. 117 (1995) 2351–2352.
5.	Chiu, H.J., Reddick, J.J., Begley, T.P. and Ealick, S.E. Crystal structure of thiamin phosphate synthase from Bacillus subtilis at 1.25 Å resolution. Biochemistry 38 (1999) 6460–6470. [DOI] [PMID: 10350464]
6.	Ajjawi, I., Tsegaye, Y. and Shintani, D. Determination of the genetic, molecular, and biochemical basis of the Arabidopsis thaliana thiamin auxotroph th1. Arch. Biochem. Biophys. 459 (2007) 107–114. [DOI] [PMID: 17174261]

[EC 2.5.1.3 created 1965, modified 2015]

*EC

2.5.1.15

Accepted name:

dihydropteroate synthase

Reaction:

(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate = diphosphate + 7,8-dihydropteroate

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

Glossary:

7,8-dihydropteroate = 4-{[(2-amino-4-oxo-3,4,7,8-tetrahydropteridin-6-yl)methyl]amino}benzoate

Other name(s):

dihydropteroate pyrophosphorylase; DHPS; 7,8-dihydropteroate synthase; 7,8-dihydropteroate synthetase; 7,8-dihydropteroic acid synthetase; dihydropteroate synthetase; dihydropteroic synthetase; 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine-diphosphate:4-aminobenzoate 2-amino-4-hydroxydihydropteridine-6-methenyltransferase; (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl-diphosphate:4-aminobenzoate 2-amino-4-hydroxydihydropteridine-6-methenyltransferase

Systematic name:

(7,8-dihydropterin-6-yl)methyl-diphosphate:4-aminobenzoate 2-amino-4-hydroxy-7,8-dihydropteridine-6-methenyltransferase

Comments:

The enzyme participates in the biosynthetic pathways for folate (in bacteria, plants and fungi) and methanopterin (in archaea). The enzyme exists in varying types of multifunctional proteins in different organisms. The enzyme from the plant Arabidopsis thaliana also harbors the activity of EC 2.7.6.3, 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase [4], while the enzyme from yeast Saccharomyces cerevisiae is trifunctional with the two above mentioned activities as well as EC 4.1.2.25, dihydroneopterin aldolase [3].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9055-61-2

References:

1.	Richey, D.P. and Brown, G.M. The biosynthesis of folic acid. IX. Purification and properties of the enzymes required for the formation of dihydropteroic acid. J. Biol. Chem. 244 (1969) 1582–1592. [PMID: 4304228]
2.	Shiota, T., Baugh, C.M., Jackson, R. and Dillard, R. The enzymatic synthesis of hydroxymethyldihydropteridine pyrophosphate and dihydrofolate. Biochemistry 8 (1969) 5022–5028. [PMID: 4312465]
3.	Güldener, U., Koehler, G.J., Haussmann, C., Bacher, A., Kricke, J., Becher, D. and Hegemann, J.H. Characterization of the Saccharomyces cerevisiae Fol1 protein: starvation for C₁ carrier induces pseudohyphal growth. Mol. Biol. Cell 15 (2004) 3811–3828. [DOI] [PMID: 15169867]
4.	Storozhenko, S., Navarrete, O., Ravanel, S., De Brouwer, V., Chaerle, P., Zhang, G.F., Bastien, O., Lambert, W., Rebeille, F. and Van Der Straeten, D. Cytosolic hydroxymethyldihydropterin pyrophosphokinase/dihydropteroate synthase from Arabidopsis thaliana: a specific role in early development and stress response. J. Biol. Chem. 282 (2007) 10749–10761. [DOI] [PMID: 17289662]

[EC 2.5.1.15 created 1972, modified 2015]

2.5.1.129

Accepted name:

flavin prenyltransferase

Reaction:

prenyl phosphate + FMNH₂ = prenylated FMNH₂ + phosphate

For diagram of prenylated FMNH₂ biosynthesis, click here

Glossary:

prenylated FMNH₂ = 3,3,4,5-tetramethyl-7-[(2S,3S,4R)-2,3,4-trihydroxy-5-(phosphonatooxy)pentyl]-2,3-dihydro-1H,7H-naphtho[1,8-fg]pteridine-9,11(8H,10H)-dione

Other name(s):

ubiX (gene name); PAD1 (gene name); dimethylallyl-phosphate:FMNH₂ prenyltransferase

Systematic name:

prenyl-phosphate:FMNH₂ prenyltransferase

Comments:

The enzyme produces the modified flavin cofactor prenylated FMNH₂, which is required by EC 4.1.1.98, 4-hydroxy-3-polyprenylbenzoate decarboxylase, and EC 4.1.1.102, phenacrylate decarboxylase. The enzyme acts as a flavin prenyltransferase, linking a prenyl moiety to the flavin N-5 and C-6 atoms and thus adding a fourth non-aromatic ring to the flavin isoalloxazine group.

Links to other databases:

References:

1.	White, M.D., Payne, K.A., Fisher, K., Marshall, S.A., Parker, D., Rattray, N.J., Trivedi, D.K., Goodacre, R., Rigby, S.E., Scrutton, N.S., Hay, S. and Leys, D. UbiX is a flavin prenyltransferase required for bacterial ubiquinone biosynthesis. Nature 522 (2015) 502–506. [DOI] [PMID: 26083743]

[EC 2.5.1.129 created 2015]

2.5.1.130

Accepted name:

2-carboxy-1,4-naphthoquinone phytyltransferase

Reaction:

phytyl diphosphate + 2-carboxy-1,4-naphthoquinone = demethylphylloquinone + diphosphate + CO₂

For diagram of vitamin K biosynthesis, click here

Glossary:

2-carboxy-1,4-naphthoquinone = 1,4-dioxo-2-naphthoic acid

Other name(s):

menA (gene name); ABC4 (gene name); 1,4-dioxo-2-naphthoate phytyltransferase; 1,4-diketo-2-naphthoate phytyltransferase

Systematic name:

phytyl-diphosphate:2-carboxy-1,4-naphthoquinone phytyltransferase

Comments:

This enzyme, found in plants and cyanobacteria, catalyses a step in the synthesis of phylloquinone (vitamin K₁), an electron carrier associated with photosystem I. The enzyme catalyses the transfer of the phytyl chain synthesized by EC 1.3.1.83, geranylgeranyl diphosphate reductase, to 2-carboxy-1,4-naphthoquinone.

Links to other databases:

References:

Johnson, T.W., Shen, G., Zybailov, B., Kolling, D., Reategui, R., Beauparlant, S., Vassiliev, I.R., Bryant, D.A., Jones, A.D., Golbeck, J.H. and Chitnis, P.R. Recruitment of a foreign quinone into the A(1) site of photosystem I. I. Genetic and physiological characterization of phylloquinone biosynthetic pathway mutants in Synechocystis sp. PCC 6803. J. Biol. Chem. 275 (2000) 8523–8530. [DOI] [PMID: 10722690]

Shimada, H., Ohno, R., Shibata, M., Ikegami, I., Onai, K., Ohto, M.A. and Takamiya, K. Inactivation and deficiency of core proteins of photosystems I and II caused by genetical phylloquinone and plastoquinone deficiency but retained lamellar structure in a T-DNA mutant of Arabidopsis. Plant J. 41 (2005) 627–637. [DOI] [PMID: 15686525]

[EC 2.5.1.130 created 2015]

2.5.1.131

Accepted name:

(4-{4-[2-(γ-L-glutamylamino)ethyl]phenoxymethyl}furan-2-yl)methanamine synthase

Reaction:

[5-(aminomethyl)furan-3-yl]methyl diphosphate + γ-L-glutamyltyramine = (4-{4-[2-(γ-L-glutamylamino)ethyl]phenoxymethyl}furan-2-yl)methanamine + diphosphate

For diagram of methanofuran biosynthesis, click here

Other name(s):

MfnF

Systematic name:

[5-(aminomethyl)furan-3-yl]methyl-diphosphate:γ-L-glutamyltyramine [5-(aminomethyl)furan-3-yl]methyltransferase

Comments:

The enzyme, isolated from the archaeon Methanocaldococcus jannaschii, participates in the biosynthesis of the methanofuran cofactor.

Links to other databases:

References:

1.	Wang, Y., Xu, H., Jones, M.K. and White, R.H. Identification of the final two genes functioning in methanofuran biosynthesis in Methanocaldococcus jannaschii. J. Bacteriol. 197 (2015) 2850–2858. [DOI] [PMID: 26100040]

[EC 2.5.1.131 created 2015]

2.7.1.190

Accepted name:

aminoglycoside 2′′-phosphotransferase

Reaction:

GTP + gentamicin = GDP + gentamicin 2′′-phosphate

Other name(s):

aphD (gene name); APH(2′′); aminoglycoside (2′′) kinase; gentamicin kinase (ambiguous); gentamicin phosphotransferase (ambiguous)

Systematic name:

GTP:gentamicin 2′′-O-phosphotransferase

Comments:

Requires Mg²⁺. This bacterial enzyme phosphorylates many 4,6-disubstituted aminoglycoside antibiotics that have a hydroxyl group at position 2′′, including kanamycin A, kanamycin B, tobramycin, dibekacin, arbekacin, amikacin, gentamicin C, sisomicin and netilmicin. In most, but not all, cases the phosphorylation confers resistance against the antibiotic. Some forms of the enzyme use ATP as a phosphate donor in appreciable amount. The enzyme is often found as a bifunctional enzyme that also catalyses 6′-aminoglycoside N-acetyltransferase activity. The bifunctional enzyme is the most clinically important aminoglycoside-modifying enzyme in Gram-positive bacteria, responsible for high-level resistance in both Enterococci and Staphylococci.

Links to other databases:

References:

1.	Ferretti, J.J., Gilmore, K.S. and Courvalin, P. Nucleotide sequence analysis of the gene specifying the bifunctional 6′-aminoglycoside acetyltransferase 2"-aminoglycoside phosphotransferase enzyme in Streptococcus faecalis and identification and cloning of gene regions specifying the two activities. J. Bacteriol. 167 (1986) 631–638. [DOI] [PMID: 3015884]
2.	Frase, H., Toth, M. and Vakulenko, S.B. Revisiting the nucleotide and aminoglycoside substrate specificity of the bifunctional aminoglycoside acetyltransferase(6′)-Ie/aminoglycoside phosphotransferase(2′′)-Ia enzyme. J. Biol. Chem. 287 (2012) 43262–43269. [DOI] [PMID: 23115238]

[EC 2.7.1.190 created 2015]

2.7.4.31

Accepted name:

[5-(aminomethyl)furan-3-yl]methyl phosphate kinase

Reaction:

ATP + [5-(aminomethyl)furan-3-yl]methyl phosphate = ADP + [5-(aminomethyl)furan-3-yl]methyl diphosphate

For diagram of methanofuran biosynthesis, click here

Other name(s):

MfnE

Systematic name:

ATP:[5-(aminomethyl)furan-3-yl]methyl-phosphate phosphotransferase

Comments:

Requires Mg²⁺. The enzyme, isolated from the archaeon Methanocaldococcus jannaschii, participates in the biosynthesis of the methanofuran cofactor.

Links to other databases:

References:

1.	Wang, Y., Xu, H., Jones, M.K. and White, R.H. Identification of the final two genes functioning in methanofuran biosynthesis in Methanocaldococcus jannaschii. J. Bacteriol. 197 (2015) 2850–2858. [DOI] [PMID: 26100040]

[EC 2.7.4.31 created 2015]

*EC

2.7.6.3

Accepted name:

2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase

Reaction:

ATP + 6-hydroxymethyl-7,8-dihydropterin = AMP + 6-hydroxymethyl-7,8-dihydropterin diphosphate

For diagram of folate biosynthesis (late stages), click here and for diagram of methanopterin biosynthesis (part 1), click here

Other name(s):

2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase; H₂-pteridine-CH2OH pyrophosphokinase; 7,8-dihydroxymethylpterin-pyrophosphokinase; HPPK; 7,8-dihydro-6-hydroxymethylpterin pyrophosphokinase; hydroxymethyldihydropteridine pyrophosphokinase; ATP:2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine 6′-diphosphotransferase

Systematic name:

ATP:6-hydroxymethyl-7,8-dihydropterin 6′-diphosphotransferase

Comments:

Binds 2 Mg²⁺ ions that are essential for activity [4]. The enzyme participates in the biosynthetic pathways for folate (in bacteria, plants, fungi, and some archaeal species, including the haloarchaea) and methanopterin (in some archaeal species such as the Archaeoglobi and Methanobacteria). The enzyme exists in varying types of multifunctional proteins in different organisms. The enzyme from the bacterium Streptococcus pneumoniae also harbours the activity of EC 4.1.2.25, dihydroneopterin aldolase [4], the enzyme from the plant Arabidopsis thaliana harbours the activity of EC 2.5.1.15, dihydropteroate synthase [7], while the enzyme from yeast Saccharomyces cerevisiae is trifunctional with both of the two above mentioned activities [6].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 37278-23-2

References:

1.	Shiota, T., Baugh, C.M., Jackson, R. and Dillard, R. The enzymatic synthesis of hydroxymethyldihydropteridine pyrophosphate and dihydrofolate. Biochemistry 8 (1969) 5022–5028. [PMID: 4312465]
2.	Richey, D.P. and Brown, G.M. The biosynthesis of folic acid. IX. Purification and properties of the enzymes required for the formation of dihydropteroic acid. J. Biol. Chem. 244 (1969) 1582–1592. [PMID: 4304228]
3.	Richey, D.P. and Brown, G.M. Hydroxymethyldihydropteridine pyrophosphokinase and dihydropteroate synthetase from Escherichia coli. Methods Enzymol. 18B (1971) 765–771.
4.	Lopez, P. and Lacks, S.A. A bifunctional protein in the folate biosynthetic pathway of Streptococcus pneumoniae with dihydroneopterin aldolase and hydroxymethyldihydropterin pyrophosphokinase activities. J. Bacteriol. 175 (1993) 2214–2220. [DOI] [PMID: 8385663]
5.	Blaszczyk, J., Shi, G., Yan, H. and Ji, X. Catalytic center assembly of HPPK as revealed by the crystal structure of a ternary complex at 1.25 Å resolution. Structure 8 (2000) 1049–1058. [DOI] [PMID: 11080626]
6.	Güldener, U., Koehler, G.J., Haussmann, C., Bacher, A., Kricke, J., Becher, D. and Hegemann, J.H. Characterization of the Saccharomyces cerevisiae Fol1 protein: starvation for C₁ carrier induces pseudohyphal growth. Mol. Biol. Cell 15 (2004) 3811–3828. [DOI] [PMID: 15169867]
7.	Storozhenko, S., Navarrete, O., Ravanel, S., De Brouwer, V., Chaerle, P., Zhang, G.F., Bastien, O., Lambert, W., Rebeille, F. and Van Der Straeten, D. Cytosolic hydroxymethyldihydropterin pyrophosphokinase/dihydropteroate synthase from Arabidopsis thaliana: a specific role in early development and stress response. J. Biol. Chem. 282 (2007) 10749–10761. [DOI] [PMID: 17289662]

[EC 2.7.6.3 created 1972, modified 2015]

*EC

2.8.1.9

Accepted name:

molybdenum cofactor sulfurtransferase

Reaction:

molybdenum cofactor + L-cysteine + reduced acceptor + 2 H⁺ = thio-molybdenum cofactor + L-alanine + H₂O + oxidized acceptor

For diagram of MoCo biosynthesis, click here

Glossary:

molybdenum cofactor = MoCo = MoO2(OH)Dtpp-mP = {[(5aR,8R,9aR)-2-amino-4-oxo-6,7-bis(sulfanyl-κS)-1,5,5a,8,9a,10-hexahydro-4H-pyrano[3,2-g]pteridin-8-yl]methyl dihydrogenato(2^-) phosphate}(dioxo)molybdate

Other name(s):

molybdenum cofactor sulfurase; ABA3; HMCS; MoCo sulfurase; MoCo sulfurtransferase

Systematic name:

L-cysteine:molybdenum cofactor sulfurtransferase

Comments:

Contains pyridoxal phosphate. Replaces the equatorial oxo ligand of the molybdenum by sulfur via an enzyme-bound persulfide. The reaction occurs in prokaryotes and eukaryotes but MoCo sulfurtransferases are only found in eukaryotes. In prokaryotes the reaction is catalysed by two enzymes: cysteine desulfurase (EC 2.8.1.7), which is homologous to the N-terminus of eukaryotic MoCo sulfurtransferases, and a molybdo-enzyme specific chaperone which binds the MoCo and acts as an adapter protein.

Links to other databases:

References:

1.	Bittner, F., Oreb, M. and Mendel, R.R. ABA3 is a molybdenum cofactor sulfurase required for activation of aldehyde oxidase and xanthine dehydrogenase in Arabidopsis thaliana. J. Biol. Chem. 276 (2001) 40381–40384. [DOI] [PMID: 11553608]
2.	Heidenreich, T., Wollers, S., Mendel, R.R. and Bittner, F. Characterization of the NifS-like domain of ABA3 from Arabidopsis thaliana provides insight into the mechanism of molybdenum cofactor sulfuration. J. Biol. Chem. 280 (2005) 4213–4218. [DOI] [PMID: 15561708]
3.	Wollers, S., Heidenreich, T., Zarepour, M., Zachmann, D., Kraft, C., Zhao, Y., Mendel, R.R. and Bittner, F. Binding of sulfurated molybdenum cofactor to the C-terminal domain of ABA3 from Arabidopsis thaliana provides insight into the mechanism of molybdenum cofactor sulfuration. J. Biol. Chem. 283 (2008) 9642–9650. [DOI] [PMID: 18258600]

[EC 2.8.1.9 created 2011, modified 2015]

3.1.3.98

Transferred entry:

geranyl diphosphate phosphohydrolase, transferred to EC 3.6.1.68, geranyl diphosphate phosphohydrolase

[EC 3.1.3.98 created 2015, deleted 2016]

3.5.1.119

Accepted name:

Pup amidohydrolase

Reaction:

[prokaryotic ubiquitin-like protein]-L-glutamine + H₂O = [prokaryotic ubiquitin-like protein]-L-glutamate + NH₃

Other name(s):

dop (gene name); Pup deamidase; depupylase/deamidase; DPUP; depupylase

Systematic name:

[prokaryotic ubiquitin-like protein]-L-glutamine amidohydrolase

Comments:

The enzyme has been characterized from the bacterium Mycobacterium tuberculosis. It catalyses the hydrolysis of the amido group of the C-terminal glutamine of prokaryotic ubiquitin-like protein (Pup), thus activating it for ligation to target proteins, a process catalysed by EC 6.3.1.19, prokaryotic ubiquitin-like protein ligase. The reaction requires ATP as cofactor but not its hydrolysis. The enzyme also catalyses the hydrolytic cleavage of the bond formed by the ligase, between an ε-amino group of a lysine residue of the target protein and the γ-carboxylate of the C-terminal glutamate of the prokaryotic ubiquitin-like protein.

Links to other databases:

References:

1.	Striebel, F., Imkamp, F., Sutter, M., Steiner, M., Mamedov, A. and Weber-Ban, E. Bacterial ubiquitin-like modifier Pup is deamidated and conjugated to substrates by distinct but homologous enzymes. Nat. Struct. Mol. Biol. 16 (2009) 647–651. [DOI] [PMID: 19448618]
2.	Burns, K.E., Cerda-Maira, F.A., Wang, T., Li, H., Bishai, W.R. and Darwin, K.H. "Depupylation" of prokaryotic ubiquitin-like protein from mycobacterial proteasome substrates. Mol. Cell 39 (2010) 821–827. [DOI] [PMID: 20705495]
3.	Striebel, F., Imkamp, F., Özcelik, D. and Weber-Ban, E. Pupylation as a signal for proteasomal degradation in bacteria. Biochim. Biophys. Acta 1843 (2014) 103–113. [DOI] [PMID: 23557784]

[EC 3.5.1.119 created 2015]

*EC

4.1.1.98

Accepted name:

4-hydroxy-3-polyprenylbenzoate decarboxylase

Reaction:

a 4-hydroxy-3-polyprenylbenzoate = a 2-polyprenylphenol + CO₂

For diagram of ubiquinol biosynthesis, click here

Other name(s):

ubiD (gene name); 4-hydroxy-3-solanesylbenzoate decarboxylase; 3-octaprenyl-4-hydroxybenzoate decarboxylase

Systematic name:

4-hydroxy-3-polyprenylbenzoate carboxy-lyase

Comments:

The enzyme catalyses a step in prokaryotic ubiquinone biosynthesis, as well as in plastoquinone biosynthesis in cyanobacteria. The enzyme can accept substrates with different polyprenyl tail lengths in vitro, but uses a specific length in vivo, which is determined by the polyprenyl diphosphate synthase that exists in the specific organism. It requires a prenylated flavin cofactor that is produced by EC 2.5.1.129, flavin prenyltransferase.

Links to other databases:

References:

1.	Leppik, R.A., Young, I.G. and Gibson, F. Membrane-associated reactions in ubiquinone biosynthesis in Escherichia coli. 3-Octaprenyl-4-hydroxybenzoate carboxy-lyase. Biochim. Biophys. Acta 436 (1976) 800–810. [DOI] [PMID: 782527]
2.	Gulmezian, M., Hyman, K.R., Marbois, B.N., Clarke, C.F. and Javor, G.T. The role of UbiX in Escherichia coli coenzyme Q biosynthesis. Arch. Biochem. Biophys. 467 (2007) 144–153. [DOI] [PMID: 17889824]
3.	Pfaff, C., Glindemann, N., Gruber, J., Frentzen, M. and Sadre, R. Chorismate pyruvate-lyase and 4-hydroxy-3-solanesylbenzoate decarboxylase are required for plastoquinone biosynthesis in the cyanobacterium Synechocystis sp. PCC6803. J. Biol. Chem. 289 (2014) 2675–2686. [DOI] [PMID: 24337576]
4.	Lin, F., Ferguson, K.L., Boyer, D.R., Lin, X.N. and Marsh, E.N. Isofunctional enzymes PAD1 and UbiX catalyze formation of a novel cofactor required by ferulic acid decarboxylase and 4-hydroxy-3-polyprenylbenzoic acid decarboxylase. ACS Chem. Biol. 10 (2015) 1137–1144. [DOI] [PMID: 25647642]
5.	Payne, K.A., White, M.D., Fisher, K., Khara, B., Bailey, S.S., Parker, D., Rattray, N.J., Trivedi, D.K., Goodacre, R., Beveridge, R., Barran, P., Rigby, S.E., Scrutton, N.S., Hay, S. and Leys, D. New cofactor supports α,β-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition. Nature 522 (2015) 497–501. [DOI] [PMID: 26083754]

[EC 4.1.1.98 created 2014, modified 2015]

4.1.1.102

Accepted name:

phenacrylate decarboxylase

Reaction:

(1) 4-coumarate = 4-vinylphenol + CO₂
(2) trans-cinnamate = styrene + CO₂
(3) ferulate = 4-vinylguaiacol + CO₂

Glossary:

4-coumarate = 3-(4-hydroxyphenyl)prop-2-enoate
trans-cinnamate = (2E)-3-phenylprop-2-enoate
ferulate = 4-hydroxy-3-methoxycinnamate

Other name(s):

FDC1 (gene name); ferulic acid decarboxylase

Systematic name:

3-phenylprop-2-enoate carboxy-lyase

Comments:

The enzyme, found in fungi, catalyses the decarboxylation of phenacrylic acids present in plant cell walls. It requires a prenylated flavin cofactor that is produced by EC 2.5.1.129, flavin prenyltransferase.

Links to other databases:

References:

1.	Mukai, N., Masaki, K., Fujii, T., Kawamukai, M. and Iefuji, H. PAD1 and FDC1 are essential for the decarboxylation of phenylacrylic acids in Saccharomyces cerevisiae. J. Biosci. Bioeng. 109 (2010) 564–569. [DOI] [PMID: 20471595]
2.	Bhuiya, M.W., Lee, S.G., Jez, J.M. and Yu, O. Structure and mechanism of ferulic acid decarboxylase (FDC1) from Saccharomyces cerevisiae. Appl. Environ. Microbiol. 81 (2015) 4216–4223. [DOI] [PMID: 25862228]
3.	Payne, K.A., White, M.D., Fisher, K., Khara, B., Bailey, S.S., Parker, D., Rattray, N.J., Trivedi, D.K., Goodacre, R., Beveridge, R., Barran, P., Rigby, S.E., Scrutton, N.S., Hay, S. and Leys, D. New cofactor supports α,β-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition. Nature 522 (2015) 497–501. [DOI] [PMID: 26083754]

[EC 4.1.1.102 created 2015]

*EC

4.1.2.25

Accepted name:

dihydroneopterin aldolase

Reaction:

7,8-dihydroneopterin = 6-(hydroxymethyl)-7,8-dihydropterin + glycolaldehyde

For diagram of folate biosynthesis (late stages), click here and for diagram of methanopterin biosynthesis (part 1), click here

Other name(s):

7,8-dihydroneopterin aldolase; 2-amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine glycolaldehyde-lyase; 2-amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine glycolaldehyde-lyase (2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine-forming); DHNA; mptD (gene name); folB (gene name)

Systematic name:

7,8-dihydroneopterin glycolaldehyde-lyase [6-(hydroxymethyl)-7,8-dihydropterin-forming]

Comments:

The enzyme participates in folate (in bacteria, plants and fungi) and methanopterin (in archaea) biosynthesis. The enzymes from the bacterium Escherichia coli and the plant Arabidopsis thaliana also catalyse the epimerisation of the 2′ hydroxy-group (EC 5.1.99.8, 7,8-dihydroneopterin epimerase) [2,3]. The enzyme from the bacterium Mycobacterium tuberculosis is trifunctional and also catalyses EC 5.1.99.8 and EC 1.13.11.81, 7,8-dihydroneopterin oxygenase [6]. The enzyme from the yeast Saccharomyces cerevisiae also catalyses the two subsequent steps in the folate biosynthesis pathway - EC 2.7.6.3, 2-amino-4-hydroxy-6-(hydroxymethyl)dihydropteridine diphosphokinase, and EC 2.5.1.15, dihydropteroate synthase [4].

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 37290-59-8

References:

1.	Mathis, J.B. and Brown, G.M. The biosynthesis of folic acid. XI. Purification and properties of dihydroneopterin aldolase. J. Biol. Chem. 245 (1970) 3015–3025. [PMID: 4912541]
2.	Haussmann, C., Rohdich, F., Schmidt, E., Bacher, A. and Richter, G. Biosynthesis of pteridines in Escherichia coli. Structural and mechanistic similarity of dihydroneopterin-triphosphate epimerase and dihydroneopterin aldolase. J. Biol. Chem. 273 (1998) 17418–17424. [DOI] [PMID: 9651328]
3.	Goyer, A., Illarionova, V., Roje, S., Fischer, M., Bacher, A. and Hanson, A.D. Folate biosynthesis in higher plants. cDNA cloning, heterologous expression, and characterization of dihydroneopterin aldolases. Plant Physiol. 135 (2004) 103–111. [DOI] [PMID: 15107504]
4.	Güldener, U., Koehler, G.J., Haussmann, C., Bacher, A., Kricke, J., Becher, D. and Hegemann, J.H. Characterization of the Saccharomyces cerevisiae Fol1 protein: starvation for C₁ carrier induces pseudohyphal growth. Mol. Biol. Cell 15 (2004) 3811–3828. [DOI] [PMID: 15169867]
5.	Czekster, C.M. and Blanchard, J.S. One substrate, five products: reactions catalyzed by the dihydroneopterin aldolase from Mycobacterium tuberculosis. J. Am. Chem. Soc. 134 (2012) 19758–19771. [DOI] [PMID: 23150985]
6.	Wang, Y., Xu, H., Grochowski, L.L. and White, R.H. Biochemical characterization of a dihydroneopterin aldolase used for methanopterin biosynthesis in methanogens. J. Bacteriol. 196 (2014) 3191–3198. [DOI] [PMID: 24982305]
7.	Blaszczyk, J., Lu, Z., Li, Y., Yan, H. and Ji, X. Crystallographic and molecular dynamics simulation analysis of Escherichia coli dihydroneopterin aldolase. Cell Biosci 4:52 (2014). [DOI] [PMID: 25264482]

[EC 4.1.2.25 created 1972, modified 2015]

*EC

4.1.2.44

Accepted name:

2,3-epoxybenzoyl-CoA dihydrolase

Reaction:

2,3-epoxy-2,3-dihydrobenzoyl-CoA + 2 H₂O = (3Z)-6-oxohex-3-enoyl-CoA + formate

For diagram of Benzoyl-CoA catabolism, click here

Glossary:

(3Z)-6-oxohex-3-enoyl-CoA = 3,4-didehydroadipyl-CoA semialdehyde

Other name(s):

2,3-dihydro-2,3-dihydroxybenzoyl-CoA lyase/hydrolase (deformylating); BoxC; dihydrodiol transforming enzyme; benzoyl-CoA oxidation component C; 2,3-dihydro-2,3-dihydroxybenzoyl-CoA 3,4-didehydroadipyl-CoA semialdehyde-lyase (formate-forming); benzoyl-CoA-dihydrodiol lyase (incorrect); 2,3-dihydro-2,3-dihydroxybenzoyl-CoA 3,4-didehydroadipyl-CoA-semialdehyde-lyase (formate-forming)

Systematic name:

2,3-epoxy-2,3-dihydrobenzoyl-CoA (3Z)-6-oxohex-3-enoyl-CoA-lyase (formate-forming)

Comments:

The enzyme is involved in the aerobic benzoyl-CoA catabolic pathway of the bacterium Azoarcus evansii. The enzyme converts 2,3-epoxy-2,3-dihydrobenzoyl-CoA to its oxepin form prior to the ring-opening and the formation of a dialdehyde intermediate.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG

References:

1.	Gescher, J., Eisenreich, W., Worth, J., Bacher, A. and Fuchs, G. Aerobic benzoyl-CoA catabolic pathway in Azoarcus evansii: studies on the non-oxygenolytic ring cleavage enzyme. Mol. Microbiol. 56 (2005) 1586–1600. [DOI] [PMID: 15916608]
2.	Rather, L.J., Knapp, B., Haehnel, W. and Fuchs, G. Coenzyme A-dependent aerobic metabolism of benzoate via epoxide formation. J. Biol. Chem. 285 (2010) 20615–20624. [DOI] [PMID: 20452977]

[EC 4.1.2.44 created 2010, modified 2015]

4.1.99.21

Transferred entry:

(5-formylfuran-3-yl)methyl phosphate synthase. Now EC 4.2.3.153 (5-formylfuran-3-yl)methyl phosphate synthase.

[EC 4.1.99.21 created 2015, deleted 2015]

4.2.1.159

Accepted name:

dTDP-4-dehydro-6-deoxy-α-D-glucopyranose 2,3-dehydratase

Reaction:

dTDP-4-dehydro-6-deoxy-α-D-glucopyranose = dTDP-3,4-didehydro-2,6-dideoxy-α-D-glucose + H₂O (overall reaction)
(1a) dTDP-4-dehydro-6-deoxy-α-D-glucopyranose = dTDP-2,6-dideoxy-D-glycero-hex-2-enos-4-ulose + H₂O
(1b) dTDP-2,6-dideoxy-D-glycero-hex-2-enos-4-ulose = dTDP-3,4-didehydro-2,6-dideoxy-α-D-glucose (spontaneous)

For diagram of dTDP-forosamine biosynthesis, click here

Other name(s):

jadO (gene name); evaA (gene name); megBVI (gene name); eryBV (gene name); mtmV (gene name); oleV (gene name); spnO (gene name); TDP-4-keto-6-deoxy-D-glucose 2,3-dehydratase; dTDP-4-dehydro-6-deoxy-α-D-glucopyranose hydro-lyase (dTDP-(2R,6S)-2,4-dihydroxy-6-methyl-2,6-dihydropyran-3-one-forming)

Systematic name:

dTDP-4-dehydro-6-deoxy-α-D-glucopyranose hydro-lyase (dTDP-2,6-dideoxy-D-glycero-hex-2-enos-4-ulose-forming)

Comments:

The enzyme participates in the biosynthesis of several deoxysugars, including β-L-4-epi-vancosamine, α-L-megosamine, L- and D-olivose, D-oliose, D-mycarose, forosamine and β-L-digitoxose. In vitro the intermediate can undergo a spontaneous decomposition to maltol [2,3].

Links to other databases:

References:

1.	Aguirrezabalaga, I., Olano, C., Allende, N., Rodriguez, L., Brana, A.F., Mendez, C. and Salas, J.A. Identification and expression of genes involved in biosynthesis of L-oleandrose and its intermediate L-olivose in the oleandomycin producer Streptomyces antibioticus. Antimicrob. Agents Chemother. 44 (2000) 1266–1275. [DOI] [PMID: 10770761]
2.	Chen, H., Thomas, M.G., Hubbard, B.K., Losey, H.C., Walsh, C.T. and Burkart, M.D. Deoxysugars in glycopeptide antibiotics: enzymatic synthesis of TDP-L-epivancosamine in chloroeremomycin biosynthesis. Proc. Natl. Acad. Sci. USA 97 (2000) 11942–11947. [DOI] [PMID: 11035791]
3.	Gonzalez, A., Remsing, L.L., Lombo, F., Fernandez, M.J., Prado, L., Brana, A.F., Kunzel, E., Rohr, J., Mendez, C. and Salas, J.A. The mtmVUC genes of the mithramycin gene cluster in Streptomyces argillaceus are involved in the biosynthesis of the sugar moieties. Mol. Gen. Genet. 264 (2001) 827–835. [PMID: 11254130]
4.	Wang, L., White, R.L. and Vining, L.C. Biosynthesis of the dideoxysugar component of jadomycin B: genes in the jad cluster of Streptomyces venezuelae ISP5230 for L-digitoxose assembly and transfer to the angucycline aglycone. Microbiology 148 (2002) 1091–1103. [DOI] [PMID: 11932454]
5.	Hong, L., Zhao, Z., Melancon, C.E., 3rd, Zhang, H. and Liu, H.W. In vitro characterization of the enzymes involved in TDP-D-forosamine biosynthesis in the spinosyn pathway of Saccharopolyspora spinosa. J. Am. Chem. Soc. 130 (2008) 4954–4967. [DOI] [PMID: 18345667]
6.	Useglio, M., Peiru, S., Rodriguez, E., Labadie, G.R., Carney, J.R. and Gramajo, H. TDP-L-megosamine biosynthesis pathway elucidation and megalomicin a production in Escherichia coli. Appl. Environ. Microbiol. 76 (2010) 3869–3877. [DOI] [PMID: 20418422]

[EC 4.2.1.159 created 2015]

4.2.1.160

Accepted name:

2,5-diamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one isomerase/dehydratase

Reaction:

2,5-diamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one = 7,8-dihydroneopterin 3′-phosphate + H₂O

Systematic name:

2,5-diamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one cyclohydrolase

Comments:

The enzyme participates in a folate biosynthesis pathway in Chlamydia.

Links to other databases:

References:

Adams, N.E., Thiaville, J.J., Proestos, J., Juarez-Vazquez, A.L., McCoy, A.J., Barona-Gomez, F., Iwata-Reuyl, D., de Crecy-Lagard, V. and Maurelli, A.T. Promiscuous and adaptable enzymes fill "holes" in the tetrahydrofolate pathway in Chlamydia species. MBio 5 (2014) e01378. [DOI] [PMID: 25006229]

[EC 4.2.1.160 created 2015]

4.2.1.161

Accepted name:

bisanhydrobacterioruberin hydratase

Reaction:

bacterioruberin = bisanhydrobacterioruberin + 2 H₂O (overall reaction)
(1a) bacterioruberin = monoanhydrobacterioruberin + H₂O
(1b) monoanhydrobacterioruberin = bisanhydrobacterioruberin + H₂O

For diagram of bacterioruberin biosynthesis, click here

Glossary:

bisanhydrobacterioruberin = 2,2′-bis(3-methylbut-2-enyl)-3,4,3′,4′-tetradehydro-1,2,1′,2′-tetrahydro-ψ,ψ-carotene-1,1′-diol
monoanhydrobacterioruberin = 2-(3-hydroxy-3-methylbutyl)-2′-(3-methylbut-2-enyl)-3,4,3′,4′-tetradehydro-1,2,1′,2′-tetrahydro-ψ,ψ-carotene-1,1′-diol

Other name(s):

CruF; C₅₀ carotenoid 2′′,3′′-hydratase

Systematic name:

bacterioruberin hydro-lyase (bisanhydrobacterioruberin-forming)

Comments:

The enzyme, isolated from the archaeon Haloarcula japonica, is involved in the biosynthesis of the C₅₀ carotenoid bacterioruberin. In this pathway it catalyses the introduction of hydroxyl groups to C3′′ and C3′′′ of bisanhydrobacterioruberin to generate bacterioruberin.

Links to other databases:

References:

1.	Yang, Y., Yatsunami, R., Ando, A., Miyoko, N., Fukui, T., Takaichi, S. and Nakamura, S. Complete biosynthetic pathway of the C₅₀ carotenoid bacterioruberin from lycopene in the extremely halophilic archaeon Haloarcula japonica. J. Bacteriol. 197 (2015) 1614–1623. [DOI] [PMID: 25712483]

[EC 4.2.1.161 created 2015]

*EC

4.2.2.3

Accepted name:

mannuronate-specific alginate lyase

Reaction:

Eliminative cleavage of alginate to give oligosaccharides with 4-deoxy-α-L-erythro-hex-4-enuronosyl groups at their non-reducing ends and β-D-mannuronate at their reducing end.

Other name(s):

alginate lyase I; alginate lyase; alginase I; alginase II; alginase; poly(β-D-1,4-mannuronide) lyase; poly(β-D-mannuronate) lyase; aly (gene name) (ambiguous); poly[(1→4)-β-D-mannuronide] lyase

Systematic name:

alginate β-D-mannuronate—uronate lyase

Comments:

The enzyme catalyses the degradation of alginate by a β-elimination reaction. It cleaves the (1→4) bond between β-D-mannuronate and either α-L-guluronate or β-D-mannuronate, generating oligosaccharides with 4-deoxy-α-L-erythro-hex-4-enuronosyl groups at their non-reducing ends and β-D-mannuronate at the reducing end. Depending on the composition of the substrate, the enzyme produces oligosaccharides ranging from two to four residues, with preference for shorter products. cf. EC 4.2.2.11, guluronate-specific alginate lyase.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9024-15-1

References:

1.	Davidson, I.W., Lawson, C.J. and Sutherland, I.W. An alginate lysate from Azotobacter vinelandii phage. J. Gen. Microbiol. 98 (1977) 223–229. [DOI] [PMID: 13144]
2.	Nakada, H.I. and Sweeny, P.C. Alginic acid degradation by eliminases from abalone hepatopancreas. J. Biol. Chem. 242 (1967) 845–851. [PMID: 6020438]
3.	Preiss, J. and Ashwell, G. Alginic acid metabolism in bacteria. I. Enzymatic formation of unsaturated oligosaccharides and 4-deoxy-L-erythro-5-hexoseulose uronic acid. J. Biol. Chem. 237 (1962) 309–316. [PMID: 14488584]

[EC 4.2.2.3 created 1965 as EC 4.2.99.4, transferred 1972 to EC 4.2.2.3, modified 1990, modified 2015]

*EC

4.2.2.11

Accepted name:

guluronate-specific alginate lyase

Reaction:

Eliminative cleavage of alginate to give oligosaccharides with 4-deoxy-α-L-erythro-hex-4-enuronosyl groups at their non-reducing ends and α-L-guluronate at their reducing end.

Other name(s):

alginase II; guluronate lyase; L-guluronan lyase; L-guluronate lyase; poly-α-L-guluronate lyase; polyguluronate-specific alginate lyase; poly(α-L-1,4-guluronide) exo-lyase; poly(α-L-guluronate) lyase; poly[(1→4)-α-L-guluronide] exo-lyase

Systematic name:

alginate α-L-guluronate—uronate lyase

Comments:

The enzyme catalyses the degradation of alginate by a β-elimination reaction. It cleaves the (1→4) bond between α-L-guluronate and either α-L-guluronate or β-D-mannuronate, generating oligosaccharides with 4-deoxy-α-L-erythro-hex-4-enuronosyl groups at their non-reducing ends and α-L-guluronate at the reducing end. Depending on the composition of the substrate, the enzyme produces oligosaccharides ranging from two to six residues, with preference for shorter products. cf. EC 4.2.2.3, mannuronate-specific alginate lyase.

Links to other databases:

BRENDA, EXPASY, KEGG, PDB, CAS registry number: 64177-88-4

References:

1.	Boyd, J. and Turvey, J.R. Isolation of poly-α-L-guluronate lyase from Klebsiella aerogenes. Carbohydr. Res. 57 (1977) 163–171. [PMID: 332364]
2.	Davidson, I.W., Sutherland, I.W. and Lawson, C.J. Purification and properties of an alginate lyase from a marine bacterium. Biochem. J. 159 (1976) 707–713. [PMID: 1008828]

[EC 4.2.2.11 created 1990, modified 2015]

4.2.2.26

Accepted name:

oligo-alginate lyase

Reaction:

Cleavage of poly(4-deoxy-α-L-erythro-hexopyranuronoside) oligosaccharides with 4-deoxy-α-L-erythro-hex-4-enopyranuronosyl groups at their non-reducing ends into 4-deoxy-α-L-erythro-hex-4-enopyranuronate monosaccharides.

Other name(s):

aly (gene name) (ambiguous); oalS17 (gene name); oligoalginate lyase; exo-oligoalginate lyase

Systematic name:

alginate oligosaccharide 4-deoxy-α-L-erythro-hex-4-enopyranuronate-(1→4)-hexananopyranuronate lyase

Comments:

The enzyme degrades unsaturated oligosaccharides produced by the action of alginate lyases (EC 4.2.2.3 and EC 4.2.2.11) on alginate, by repeatedly removing the unsaturated residue from the non-reducing end until only unsaturated monosaccharides are left. The enzyme catalyses a β-elimination reaction, generating a new unsaturated non-reducing end after removal of the pre-existing one.

Links to other databases:

References:

1.	Hashimoto, W., Miyake, O., Momma, K., Kawai, S. and Murata, K. Molecular identification of oligoalginate lyase of Sphingomonas sp. strain A1 as one of the enzymes required for complete depolymerization of alginate. J. Bacteriol. 182 (2000) 4572–4577. [DOI] [PMID: 10913091]
2.	Kim, H.T., Chung, J.H., Wang, D., Lee, J., Woo, H.C., Choi, I.G. and Kim, K.H. Depolymerization of alginate into a monomeric sugar acid using Alg17C, an exo-oligoalginate lyase cloned from Saccharophagus degradans 2-40. Appl. Microbiol. Biotechnol. 93 (2012) 2233–2239. [DOI] [PMID: 22281843]
3.	Jagtap, S.S., Hehemann, J.H., Polz, M.F., Lee, J.K. and Zhao, H. Comparative biochemical characterization of three exolytic oligoalginate lyases from Vibrio splendidus reveals complementary substrate scope, temperature, and pH adaptations. Appl. Environ. Microbiol. 80 (2014) 4207–4214. [DOI] [PMID: 24795372]
4.	Wang, L., Li, S., Yu, W. and Gong, Q. Cloning, overexpression and characterization of a new oligoalginate lyase from a marine bacterium, Shewanella sp. Biotechnol. Lett. 37 (2015) 665–671. [DOI] [PMID: 25335746]

[EC 4.2.2.26 created 2015]

4.2.3.153

Accepted name:

(5-formylfuran-3-yl)methyl phosphate synthase

Reaction:

2 D-glyceraldehyde 3-phosphate = (5-formylfuran-3-yl)methyl phosphate + phosphate + 2 H₂O

For diagram of methanofuran biosynthesis, click here

Glossary:

(5-formylfuran-3-yl)methyl phosphate = 4-(hydroxymethyl)furan-2-carboxaldehyde phosphate

Other name(s):

mfnB (gene name); 4-HFC-P synthase; 4-(hydroxymethyl)-2-furaldehyde phosphate synthase

Systematic name:

D-glyceraldehyde-3-phosphate phosphate-lyase [D-glyceraldehyde-3-phosphate-adding; (5-formylfuran-3-yl)methyl-phosphate-forming]

Comments:

The enzyme catalyses the reaction in the direction of producing (5-formylfuran-3-yl)methyl phosphate, an intermediate in the biosynthesis of methanofuran. The sequence of events starts with the removal of a phosphate group, followed by aldol condensation and cyclization. Methanofuran is a carbon-carrier cofactor involved in the first step of the methanogenic reduction of carbon dioxide by methanogenic archaea.

Links to other databases:

References:

1.	Miller, D., Wang, Y., Xu, H., Harich, K. and White, R.H. Biosynthesis of the 5-(aminomethyl)-3-furanmethanol moiety of methanofuran. Biochemistry 53 (2014) 4635–4647. [DOI] [PMID: 24977328]
2.	Bobik, T.A., Morales, E.J., Shin, A., Cascio, D., Sawaya, M.R., Arbing, M., Yeates, T.O. and Rasche, M.E. Structure of the methanofuran/methanopterin-biosynthetic enzyme MJ1099 from Methanocaldococcus jannaschii. Acta Crystallogr. F Struct. Biol. Commun. 70 (2014) 1472–1479. [DOI] [PMID: 25372812]
3.	Wang, Y., Jones, M.K., Xu, H., Ray, W.K. and White, R.H. Mechanism of the enzymatic synthesis of 4-(hydroxymethyl)-2-furancarboxaldehyde-phosphate (4-HFC-P) from glyceraldehyde-3-phosphate catalyzed by 4-HFC-P synthase. Biochemistry 54 (2015) 2997–3008. [DOI] [PMID: 25905665]

[EC 4.2.3.153 created 2015 as EC 4.1.99.21, transferred 2015 to EC 4.2.3.153]

*EC

5.1.3.17

Accepted name:

heparosan-N-sulfate-glucuronate 5-epimerase

Reaction:

Epimerization of D-glucuronate in heparosan-N-sulfate to L-iduronate.

Other name(s):

heparosan epimerase; heparosan-N-sulfate-D-glucuronosyl 5-epimerase; C-5 uronosyl epimerase; polyglucuronate epimerase; D-glucuronyl C-5 epimerase; poly[(1,4)-β-D-glucuronosyl-(1,4)-N-sulfo-α-D-glucosaminyl] glucurono-5-epimerase

Systematic name:

poly[(1→4)-β-D-glucuronosyl-(1→4)-N-sulfo-α-D-glucosaminyl] glucurono-5-epimerase

Comments:

The enzyme acts on D-glucosyluronate residues in N-sulfated heparosan polymers, converting them to L-iduronate, thus modifying the polymer to heparan-N-sulfate. The enzyme requires that at least the N-acetylglucosamine residue linked to C-4 of the substrate has been deacetylated and N-sulfated, and activity is highest with fully N-sulfated substrate. It does not act on glucuronate residues that are O-sulfated or are adjacent to N-acetylglucosamine residues that are O-sulfated at the 6 position. Thus the epimerization from D-glucuronate to L-iduronate occurs after N-sulfation of glucosamine residues but before O-sulfation. Not identical with EC 5.1.3.19 chondroitin-glucuronate 5-epimerase or with EC 5.1.3.36, heparosan-glucuronate 5-epimerase.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 112567-86-9

References:

1.	Jacobsson, I., Bäckström, G., Höök, M., Lindahl, U., Feingold, D.S., Malmström, A. and Rodén, L. Biosynthesis of heparin. Assay and properties of the microsomal uronosyl C-5 epimerase. J. Biol. Chem. 254 (1979) 2975–2982. [PMID: 107165]
2.	Jacobsson, I., Lindahl, U., Jensen, J.W., Roden, L., Prihar, H. and Feingold, D.S. Biosynthesis of heparin. Substrate specificity of heparosan N-sulfate D-glucuronosyl 5-epimerase. J. Biol. Chem. 259 (1984) 1056–1063. [PMID: 6420398]
3.	Hagner-McWhirter, A., Hannesson, H.H., Campbell, P., Westley, J., Roden, L., Lindahl, U. and Li, J.P. Biosynthesis of heparin/heparan sulfate: kinetic studies of the glucuronyl C⁵-epimerase with N-sulfated derivatives of the Escherichia coli K5 capsular polysaccharide as substrates. Glycobiology 10 (2000) 159–171. [DOI] [PMID: 10642607]

[EC 5.1.3.17 created 1984, modified 2015]

5.1.3.36

Accepted name:

heparosan-glucuronate 5-epimerase

Reaction:

[heparosan]-D-glucuronate = [acharan]-L-iduronate

Glossary:

acharan = [GlcNAc-α-(1→4)-IdoA-α-(1→4)]_n
heparosan = [GlcNAc-α-(1→4)-GlcA-β-(1→4)]_n

Other name(s):

HG-5epi

Systematic name:

[heparosan]-D-glucuronate 5-epimerase

Comments:

The enzyme, characterized from the giant African snail Achatina fulica, participates in the biosynthetic pathway of acharan sulfate. Unlike EC 5.1.3.17, heparosan-N-sulfate-glucuronate 5-epimerase, it shows no activity with D-glucuronate residues in heparosan-N-sulfate.

Links to other databases:

References:

1.	Mochizuki, H., Yamagishi, K., Suzuki, K., Kim, Y.S. and Kimata, K. Heparosan-glucuronate 5-epimerase: Molecular cloning and characterization of a novel enzyme. Glycobiology 25 (2015) 735–744. [DOI] [PMID: 25677302]

[EC 5.1.3.36 created 2015]

5.1.3.37

Accepted name:

mannuronan 5-epimerase

Reaction:

[mannuronan]-β-D-mannuronate = [alginate]-α-L-guluronate

Glossary:

mannuronan = a linear polymer of β-D-mannuronate residues linked by (1-4) linkages
alginate = a linear polymer of β-D-mannuronate residues linked by (1-4) linkages, with variable amounts of its C-5 epimer α-L-guluronate.

Other name(s):

algG (gene name); alginate epimerase; C⁵-mannuronan epimerase; mannuronan C-5-epimerase

Systematic name:

[mannuronan]-β-D-mannuronate 5-epimerase

Comments:

The enzyme epimerizes the C-5 bond in some β-D-mannuronate residues in mannuronan, converting them to α-L-guluronate residues, and thus modifying the mannuronan into alginate. It is found in brown algae and alginate-producing bacterial species from the Pseudomonas and Azotobacter genera.

Links to other databases:

References:

1.	Franklin, M.J., Chitnis, C.E., Gacesa, P., Sonesson, A., White, D.C. and Ohman, D.E. Pseudomonas aeruginosa AlgG is a polymer level alginate C⁵-mannuronan epimerase. J. Bacteriol. 176 (1994) 1821–1830. [DOI] [PMID: 8144447]
2.	Morea, A., Mathee, K., Franklin, M.J., Giacomini, A., O'Regan, M. and Ohman, D.E. Characterization of algG encoding C⁵-epimerase in the alginate biosynthetic gene cluster of Pseudomonas fluorescens. Gene 278 (2001) 107–114. [DOI] [PMID: 11707327]
3.	Nyvall, P., Corre, E., Boisset, C., Barbeyron, T., Rousvoal, S., Scornet, D., Kloareg, B. and Boyen, C. Characterization of mannuronan C-5-epimerase genes from the brown alga Laminaria digitata. Plant Physiol. 133 (2003) 726–735. [DOI] [PMID: 14526115]
4.	Jain, S., Franklin, M.J., Ertesvag, H., Valla, S. and Ohman, D.E. The dual roles of AlgG in C-5-epimerization and secretion of alginate polymers in Pseudomonas aeruginosa. Mol. Microbiol. 47 (2003) 1123–1133. [DOI] [PMID: 12581364]
5.	Douthit, S.A., Dlakic, M., Ohman, D.E. and Franklin, M.J. Epimerase active domain of Pseudomonas aeruginosa AlgG, a protein that contains a right-handed β-helix. J. Bacteriol. 187 (2005) 4573–4583. [DOI] [PMID: 15968068]
6.	Wolfram, F., Kitova, E.N., Robinson, H., Walvoort, M.T., Codee, J.D., Klassen, J.S. and Howell, P.L. Catalytic mechanism and mode of action of the periplasmic alginate epimerase AlgG. J. Biol. Chem. 289 (2014) 6006–6019. [DOI] [PMID: 24398681]

[EC 5.1.3.37 created 2015]

5.1.99.8

Accepted name:

7,8-dihydroneopterin epimerase

Reaction:

7,8-dihydroneopterin = 7,8-dihydromonapterin

Glossary:

7,8-dihydroneopterin = 2-amino-6-[(1S,2R)-1,2,3-trihydroxypropyl]-7,8-dihydropteridin-4(3H)-one
7,8-dihydromonapterin = 2-amino-6-[(1S,2S)-1,2,3-trihydroxypropyl]-7,8-dihydropteridin-4(3H)-one

Systematic name:

7,8-dihydroneopterin 2′-epimerase

Comments:

The enzyme, which has been characterized in bacteria and plants, also has the activity of EC 4.1.2.25, dihydroneopterin aldolase. The enzyme from the bacterium Mycobacterium tuberculosis has an additional oxygenase function (EC 1.13.11.81, 7,8-dihydroneopterin oxygenase) [4].

Links to other databases:

References:

1.	Haussmann, C., Rohdich, F., Schmidt, E., Bacher, A. and Richter, G. Biosynthesis of pteridines in Escherichia coli. Structural and mechanistic similarity of dihydroneopterin-triphosphate epimerase and dihydroneopterin aldolase. J. Biol. Chem. 273 (1998) 17418–17424. [DOI] [PMID: 9651328]
2.	Goyer, A., Illarionova, V., Roje, S., Fischer, M., Bacher, A. and Hanson, A.D. Folate biosynthesis in higher plants. cDNA cloning, heterologous expression, and characterization of dihydroneopterin aldolases. Plant Physiol. 135 (2004) 103–111. [DOI] [PMID: 15107504]
3.	Czekster, C.M. and Blanchard, J.S. One substrate, five products: reactions catalyzed by the dihydroneopterin aldolase from Mycobacterium tuberculosis. J. Am. Chem. Soc. 134 (2012) 19758–19771. [DOI] [PMID: 23150985]
4.	Blaszczyk, J., Lu, Z., Li, Y., Yan, H. and Ji, X. Crystallographic and molecular dynamics simulation analysis of Escherichia coli dihydroneopterin aldolase. Cell Biosci 4:52 (2014). [DOI] [PMID: 25264482]

[EC 5.1.99.8 created 2015]

*EC

5.5.1.25

Accepted name:

3,6-anhydro-L-galactonate cycloisomerase

Reaction:

3,6-anhydro-L-galactonate = 2-dehydro-3-deoxy-L-galactonate

Other name(s):

3,6-anhydro-α-L-galactonate lyase (ring-opening); 3,6-anhydro-α-L-galactonate cycloisomerase

Systematic name:

3,6-anhydro-L-galactonate lyase (ring-opening)

Comments:

The enzyme, characterized from the marine bacteria Vibrio sp. EJY3 and Postechiella marina M091, is involved in a degradation pathway for 3,6-anhydro-α-L-galactopyranose, a major component of the polysaccharides of red macroalgae.

Links to other databases:

References:

1.	Yun, E.J., Lee, S., Kim, H.T., Pelton, J.G., Kim, S., Ko, H.J., Choi, I.G. and Kim, K.H. The novel catabolic pathway of 3,6-anhydro-L-galactose, the main component of red macroalgae, in a marine bacterium. Environ. Microbiol. 17 (2015) 1677–1688. [DOI] [PMID: 25156229]
2.	Lee, S.B., Cho, S.J., Kim, J.A., Lee, S.Y., Kim, S.M. and Lim, H.S. Metabolic pathway of 3,6-anhydro-L-galactose in agar-degrading microorganisms. Biotechnol. Bioprocess Eng. 19 (2014) 866–878.

[EC 5.5.1.25 created 2014, modified 2015]

6.3.1.19

Accepted name:

prokaryotic ubiquitin-like protein ligase

Reaction:

ATP + [prokaryotic ubiquitin-like protein]-L-glutamate + [protein]-L-lysine = ADP + phosphate + N⁶-([prokaryotic ubiquitin-like protein]-γ-L-glutamyl)-[protein]-L-lysine

Other name(s):

PafA (ambiguous); Pup ligase; proteasome accessory factor A

Systematic name:

[prokaryotic ubiquitin-like protein]:[protein]-L-lysine

Comments:

The enzyme has been characterized from the bacteria Mycobacterium tuberculosis and Corynebacterium glutamicum. It catalyses the ligation of the prokaryotic ubiquitin-like protein (Pup) to a target protein by forming a bond between an ε-amino group of a lysine residue of the target protein and the γ-carboxylate of the C-terminal glutamate of the ubiquitin-like protein (Pup). The attachment of Pup, also known as Pupylation, marks proteins for proteasomal degradation.

Links to other databases: