Proposed Changes to the Enzyme List

References:

1.	Baker, D.P. and Fewson, C.A. Purification and characterization of D(–)-mandelate dehydrogenase from Rhodotorula graminis. Microbiology 135 (1989) 2035–2044.
2.	Baker, D.P., Kleanthous, C., Keen, J.N., Weinhold, E. and Fewson, C.A. Mechanistic and active-site studies on D(–)-mandelate dehydrogenase from Rhodotorula graminis. Biochem. J. 281 (1992) 211–218. [PMID: 1731758]

[EC 1.1.1.379 created 2014]

1.1.1.380

Accepted name:

L-gulonate 5-dehydrogenase

Reaction:

L-gulonate + NAD⁺ = D-fructuronate + NADH + H⁺

Glossary:

D-fructuronate = D-arabino-hexuronate

Systematic name:

L-gulonate:NAD⁺ 5-oxidoreductase

Comments:

The enzyme, characterized from the bacterium Halomonas elongata, participates in a pathway for L-gulonate degradation.

Links to other databases:

References:

1.	Cooper, R.A. The pathway for L-gulonate catabolism in Escherichia coli K-12 and Salmonella typhimurium LT-2. FEBS Lett. 115 (1980) 63–67. [DOI] [PMID: 6993236]
2.	Wichelecki, D.J., Vendiola, J.A., Jones, A.M., Al-Obaidi, N., Almo, S.C. and Gerlt, J.A. Investigating the physiological roles of low-efficiency D-mannonate and D-gluconate dehydratases in the enolase superfamily: pathways for the catabolism of L-gulonate and L-idonate. Biochemistry 53 (2014) 5692–5699. [DOI] [PMID: 25145794]

[EC 1.1.1.380 created 2014]

1.1.1.381

Accepted name:

3-hydroxy acid dehydrogenase

Reaction:

L-allo-threonine + NADP⁺ = aminoacetone + CO₂ + NADPH + H⁺ (overall reaction)
(1a) L-allo-threonine + NADP⁺ = L-2-amino-3-oxobutanoate + NADPH + H⁺
(1b) L-2-amino-3-oxobutanoate = aminoacetone + CO₂ (spontaneous)

Glossary:

L-allo-threonine = (2S,3S)-2-amino-3-hydroxybutanoic acid
aminoacetone = 1-aminopropan-2-one
L-2-amino-3-oxobutanoate = (2S)-2-amino-3-oxobutanoate

Other name(s):

ydfG (gene name); YMR226c (gene name)

Systematic name:

L-allo-threonine:NADP⁺ 3-oxidoreductase

Comments:

The enzyme, purified from the bacterium Escherichia coli and the yeast Saccharomyces cerevisiae, shows activity with a range of 3- and 4-carbon 3-hydroxy acids. The highest activity is seen with L-allo-threonine and D-threonine. The enzyme from Escherichia coli also shows high activity with L-serine, D-serine, (S)-3-hydroxy-2-methylpropanoate and (R)-3-hydroxy-2-methylpropanoate. The enzyme has no activity with NAD⁺ or L-threonine (cf. EC 1.1.1.103, L-threonine 3-dehydrogenase).

Links to other databases:

References:

1.	Fujisawa, H., Nagata, S. and Misono, H. Characterization of short-chain dehydrogenase/reductase homologues of Escherichia coli (YdfG) and Saccharomyces cerevisiae (YMR226C). Biochim. Biophys. Acta 1645 (2003) 89–94. [DOI] [PMID: 12535615]

[EC 1.1.1.381 created 2014, modified 2015]

1.1.3.47

Accepted name:

5-(hydroxymethyl)furfural oxidase

Reaction:

5-(hydroxymethyl)furfural + 3 O₂ + 2 H₂O = furan-2,5-dicarboxylate + 3 H₂O₂ (overall reaction)
(1a) 5-(hydroxymethyl)furfural + O₂ = furan-2,5-dicarbaldehyde + H₂O₂
(1b) furan-2,5-dicarbaldehyde + H₂O = 5-(dihydroxymethyl)furan-2-carbaldehyde (spontaneous)
(1c) 5-(dihydroxymethyl)furan-2-carbaldehyde + O₂ = 5-formylfuran-2-carboxylate + H₂O₂
(1d) 5-formylfuran-2-carboxylate + H₂O = 5-(dihydroxymethyl)furan-2-carboxylate (spontaneous)
(1e) 5-(dihydroxymethyl)furan-2-carboxylate + O₂ = furan-2,5-dicarboxylate + H₂O₂

Glossary:

5-(hydroxymethyl)furfural = 5-(hydroxymethyl)furan-2-carbaldehyde

Systematic name:

5-(hydroxymethyl)furfural:oxygen oxidoreductase

Comments:

The enzyme, characterized from the bacterium Methylovorus sp. strain MP688, is involved in the degradation and detoxification of 5-(hydroxymethyl)furfural. The enzyme acts only on alcohol groups and requires the spontaneous hydration of aldehyde groups for their oxidation [3]. The enzyme has a broad substrate range that overlaps with EC 1.1.3.7, aryl-alcohol oxidase.

Links to other databases:

References:

1.	Koopman, F., Wierckx, N., de Winde, J.H. and Ruijssenaars, H.J. Identification and characterization of the furfural and 5-(hydroxymethyl)furfural degradation pathways of Cupriavidus basilensis HMF14. Proc. Natl. Acad. Sci. USA 107 (2010) 4919–4924. [DOI] [PMID: 20194784]
2.	Dijkman, W.P. and Fraaije, M.W. Discovery and characterization of a 5-hydroxymethylfurfural oxidase from Methylovorus sp. strain MP688. Appl. Environ. Microbiol. 80 (2014) 1082–1090. [DOI] [PMID: 24271187]
3.	Dijkman, W.P., Groothuis, D.E. and Fraaije, M.W. Enzyme-catalyzed oxidation of 5-hydroxymethylfurfural to furan-2,5-dicarboxylic acid. Angew. Chem. Int. Ed. Engl. 53 (2014) 6515–6518. [DOI] [PMID: 24802551]

[EC 1.1.3.47 created 2014]

1.1.4.1

Transferred entry:

vitamin-K-epoxide reductase (warfarin-sensitive). Now EC 1.17.4.4, vitamin-K-epoxide reductase (warfarin-sensitive)

[EC 1.1.4.1 created 1989, deleted 2014]

1.1.4.2

Transferred entry:

vitamin-K-epoxide reductase (warfarin-insensitive). Now EC 1.17.4.5, vitamin-K-epoxide reductase (warfarin-insensitive)

[EC 1.1.4.2 created 1989, deleted 2014]

1.2.1.90

Accepted name:

glyceraldehyde-3-phosphate dehydrogenase [NAD(P)⁺]

Reaction:

D-glyceraldehyde 3-phosphate + NAD(P)⁺ + H₂O = 3-phospho-D-glycerate + NAD(P)H + 2 H⁺

Other name(s):

non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (ambiguous); GAPN

Systematic name:

D-glyceraldehyde-3-phosphate:NAD(P)⁺ oxidoreductase

Comments:

The enzyme is part of the modified Embden-Meyerhof-Parnas pathway of the archaeon Thermoproteus tenax. cf. EC 1.2.1.9 [glyceraldehyde-3-phosphate dehydrogenase (NADP⁺)].

Links to other databases:

References:

1.	Brunner, N.A., Brinkmann, H., Siebers, B. and Hensel, R. NAD⁺-dependent glyceraldehyde-3-phosphate dehydrogenase from Thermoproteus tenax. The first identified archaeal member of the aldehyde dehydrogenase superfamily is a glycolytic enzyme with unusual regulatory properties. J. Biol. Chem. 273 (1998) 6149–6156. [DOI] [PMID: 9497334]
2.	Brunner, N.A., Siebers, B. and Hensel, R. Role of two different glyceraldehyde-3-phosphate dehydrogenases in controlling the reversible Embden-Meyerhof-Parnas pathway in Thermoproteus tenax: regulation on protein and transcript level. Extremophiles 5 (2001) 101–109. [PMID: 11354453]
3.	Pohl, E., Brunner, N., Wilmanns, M. and Hensel, R. The crystal structure of the allosteric non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic archaeum Thermoproteus tenax. J. Biol. Chem. 277 (2002) 19938–19945. [DOI] [PMID: 11842090]
4.	Lorentzen, E., Hensel, R., Knura, T., Ahmed, H. and Pohl, E. Structural basis of allosteric regulation and substrate specificity of the non-phosphorylating glyceraldehyde 3-phosphate dehydrogenase from Thermoproteus tenax. J. Mol. Biol. 341 (2004) 815–828. [DOI] [PMID: 15288789]

[EC 1.2.1.90 created 2014]

1.2.1.91

Accepted name:

3-oxo-5,6-dehydrosuberyl-CoA semialdehyde dehydrogenase

Reaction:

3-oxo-5,6-dehydrosuberyl-CoA semialdehyde + NADP⁺ + H₂O = 3-oxo-5,6-dehydrosuberyl-CoA + NADPH + H⁺

For diagram of aerobic phenylacetate catabolism, click here

Glossary:

3-oxo-5,6-dehydrosuberyl-CoA semialdehyde = 3,8-dioxooct-5-enoyl-CoA

Other name(s):

paaZ (gene name)

Systematic name:

3-oxo-5,6-dehydrosuberyl-CoA semialdehyde:NADP⁺ oxidoreductase

Comments:

The enzyme from Escherichia coli is a bifunctional fusion protein that also catalyses EC 3.3.2.12, oxepin-CoA hydrolase. Combined the two activities result in a two-step conversion of oxepin-CoA to 3-oxo-5,6-dehydrosuberyl-CoA, part of an aerobic phenylacetate degradation pathway.

Links to other databases:

References:

1.	Ferrandez, A., Minambres, B., Garcia, B., Olivera, E.R., Luengo, J.M., Garcia, J.L. and Diaz, E. Catabolism of phenylacetic acid in Escherichia coli. Characterization of a new aerobic hybrid pathway. J. Biol. Chem. 273 (1998) 25974–25986. [DOI] [PMID: 9748275]
2.	Ismail, W., El-Said Mohamed, M., Wanner, B.L., Datsenko, K.A., Eisenreich, W., Rohdich, F., Bacher, A. and Fuchs, G. Functional genomics by NMR spectroscopy. Phenylacetate catabolism in Escherichia coli. Eur. J. Biochem. 270 (2003) 3047–3054. [DOI] [PMID: 12846838]
3.	Teufel, R., Mascaraque, V., Ismail, W., Voss, M., Perera, J., Eisenreich, W., Haehnel, W. and Fuchs, G. Bacterial phenylalanine and phenylacetate catabolic pathway revealed. Proc. Natl. Acad. Sci. USA 107 (2010) 14390–14395. [DOI] [PMID: 20660314]

[EC 1.2.1.91 created 2011 as EC 1.17.1.7, transferred 2014 to EC 1.2.1.91]

1.2.1.92

Accepted name:

3,6-anhydro-α-L-galactose dehydrogenase

Reaction:

3,6-anhydro-α-L-galactopyranose + NAD(P)⁺ + H₂O = 3,6-anhydro-L-galactonate + NAD(P)H + H⁺

Systematic name:

3,6-anhydro-α-L-galactopyranose:NAD(P)⁺ 1-oxidoredutase

Comments:

The enzyme, characterized from the marine bacterium Vibrio sp. EJY3, is involved in a degradation pathway for 3,6-anhydro-α-L-galactose, a major component of the polysaccharides produced by red macroalgae, such as agarose and porphyran.

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 (2014) 1677–1688. [DOI] [PMID: 25156229]

[EC 1.2.1.92 created 2014]

1.9 Acting on a heme group of donors

1.9.98 With other, known, acceptors

1.9.98.1

Accepted name:

iron—cytochrome-c reductase

Reaction:

ferrocytochrome c + Fe³⁺ = ferricytochrome c + Fe²⁺

Other name(s):

iron-cytochrome c reductase

Systematic name:

ferrocytochrome-c:Fe³⁺ oxidoreductase

Comments:

An iron protein.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 37256-52-3

References:

1.	Yates, M.G. and Nason, A. Electron transport systems of the chemoautotroph Ferrobacillus ferrooxidans. II. Purification and properties of a heat-labile iron-cytochrome c reductase. J. Biol. Chem. 241 (1966) 4872–4880. [PMID: 4288725]

[EC 1.9.98.1 created 1972 as EC 1.9.99.1, transferred 2014 to EC 1.9.98.1]

1.9.99.1

Transferred entry:

iron—cytochrome-c reductase. Now EC 1.9.98.1, iron—cytochrome-c reductase

[EC 1.9.99.1 created 1972, deleted 2014]

*EC

1.14.99.42

Transferred entry:

zeaxanthin 7,8-dioxygenase. Now EC 1.13.11.84, crocetin dialdehyde synthase

[EC 1.14.99.42 created 2011, modified 2014, deleted 2017]

1.17.1.7

Transferred entry:

3-oxo-5,6-dehydrosuberyl-CoA semialdehyde dehydrogenase. Now EC 1.2.1.91, 3-oxo-5,6-dehydrosuberyl-CoA semialdehyde dehydrogenase

[EC 1.17.1.7 created 2011, deleted 2014]

1.17.4.4

Accepted name:

vitamin-K-epoxide reductase (warfarin-sensitive)

Reaction:

(1) phylloquinone + a protein with a disulfide bond + H₂O = 2,3-epoxyphylloquinone + a protein with reduced L-cysteine residues
(2) phylloquinol + a protein with a disulfide bond = phylloquinone + a protein with reduced L-cysteine residues

For diagram of the vitamin K cycle, click here

Glossary:

phylloquinone = vitamin K₁ = 2-methyl-3-phytyl-1,4-naphthoquinone
2,3-epoxyphylloquinone = vitamin K₁ 2,3-epoxide = 2,3-epoxy-2-methyl-3-phytyl-2,3-dihydro-1,4-naphthoquinone

Other name(s):

VKORC1 (gene name); VKORC1L1 (gene name)

Systematic name:

phylloquinone:disulfide oxidoreductase

Comments:

The enzyme catalyses the reduction of vitamin K 2,3-epoxide, which is formed by the activity of EC 4.1.1.90, peptidyl-glutamate 4-carboxylase, back to its phylloquinol active form. The enzyme forms a tight complex with EC 5.3.4.1, protein disulfide-isomerase, which transfers the required electrons from newly-synthesized proteins by catalysing the formation of disulfide bridges. The enzyme acts on the epoxide forms of both phylloquinone (vitamin K₁) and menaquinone (vitamin K₂). Inhibited strongly by (S)-warfarin and ferulenol.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 55963-40-1

References:

1.	Whitlon, D.S., Sadowski, J.A. and Suttie, J.W. Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. Biochemistry 17 (1978) 1371–1377. [PMID: 646989]
2.	Lee, J.L. and Fasco, M.J. Metabolism of vitamin K and vitamin K 2,3-epoxide via interaction with a common disulfide. Biochemistry 23 (1984) 2246–2252. [PMID: 6733086]
3.	Mukharji, I. and Silverman, R.B. Purification of a vitamin K epoxide reductase that catalyzes conversion of vitamin K 2,3-epoxide to 3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone. Proc. Natl. Acad. Sci. USA 82 (1985) 2713–2717. [DOI] [PMID: 3857611]
4.	Li, T., Chang, C.Y., Jin, D.Y., Lin, P.J., Khvorova, A. and Stafford, D.W. Identification of the gene for vitamin K epoxide reductase. Nature 427 (2004) 541–544. [PMID: 14765195]
5.	Wajih, N., Hutson, S.M. and Wallin, R. Disulfide-dependent protein folding is linked to operation of the vitamin K cycle in the endoplasmic reticulum. A protein disulfide isomerase-VKORC1 redox enzyme complex appears to be responsible for vitamin K₁ 2,3-epoxide reduction. J. Biol. Chem. 282 (2007) 2626–2635. [PMID: 17124179]
6.	Spohn, G., Kleinridders, A., Wunderlich, F.T., Watzka, M., Zaucke, F., Blumbach, K., Geisen, C., Seifried, E., Muller, C., Paulsson, M., Bruning, J.C. and Oldenburg, J. VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding. Thromb Haemost 101 (2009) 1044–1050. [PMID: 19492146]
7.	Schulman, S., Wang, B., Li, W. and Rapoport, T.A. Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox partners. Proc. Natl. Acad. Sci. USA 107 (2010) 15027–15032. [PMID: 20696932]

[EC 1.17.4.4 created 1989 as EC 1.1.4.1, transferred 2014 to EC 1.17.4.4, modified 2018]

1.17.4.5

Accepted name:

vitamin-K-epoxide reductase (warfarin-insensitive)

Reaction:

3-hydroxy-2-methyl-3-phytyl-2,3-dihydro-1,4-naphthoquinone + oxidized dithiothreitol = 2,3-epoxy-2-methyl-3-phytyl-2,3-dihydro-1,4-naphthoquinone + 1,4-dithiothreitol

Glossary:

2,3-epoxy-2-methyl-3-phytyl-2,3-dihydro-1,4-naphthoquinone = vitamin K 2,3-epoxide

Systematic name:

3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone:oxidized-dithiothreitol oxidoreductase

Comments:

Vitamin K 2,3-epoxide is reduced to 3-hydroxy- (and 2-hydroxy-) vitamin K by 1,4-dithiothreitol, which is oxidized to a disulfide. Not inhibited by warfarin [cf. EC 1.17.4.4, vitamin-K-epoxide reductase (warfarin-sensitive)].

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 97089-80-0

References:

1.	Mukharji, I. and Silverman, R.B. Purification of a vitamin K epoxide reductase that catalyzes conversion of vitamin K 2,3-epoxide to 3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone. Proc. Natl. Acad. Sci. USA 82 (1985) 2713–2717. [DOI] [PMID: 3857611]

[EC 1.17.4.5 created 1989 as EC 1.1.4.2, transferred 2014 to EC 1.17.4.5]

*EC

1.17.7.1

Accepted name:

(E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase (ferredoxin)

Reaction:

(E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + H₂O + 2 oxidized ferredoxin = 2-C-methyl-D-erythritol 2,4-cyclodiphosphate + 2 reduced ferredoxin

For diagram of Non-Mevalonate terpenoid biosynthesis, click here

Other name(s):

4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (ambiguous); (E)-4-hydroxy-3-methylbut-2-en-1-yl-diphosphate:protein-disulfide oxidoreductase (hydrating) (incorrect); (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase (ambiguous); gcpE (gene name); ISPG (gene name); (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase

Systematic name:

(E)-4-hydroxy-3-methylbut-2-en-1-yl-diphosphate:oxidized ferredoxin oxidoreductase

Comments:

An iron-sulfur protein found in plant chloroplasts and cyanobacteria that contains a [4Fe-4S] cluster [1]. Forms part of an alternative non-mevalonate pathway for isoprenoid biosynthesis. Bacteria have a similar enzyme that uses flavodoxin rather than ferredoxin (cf. EC 1.17.7.3). The enzyme from the plant Arabidopsis thaliana is active with photoreduced 5-deazaflavin but not with flavodoxin [1].

Links to other databases:

References:

1.	Okada, K. and Hase, T. Cyanobacterial non-mevalonate pathway: (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase interacts with ferredoxin in Thermosynechococcus elongatus BP-1. J. Biol. Chem. 280 (2005) 20672–20679. [DOI] [PMID: 15792953]
2.	Seemann, M., Wegner, P., Schünemann, V., Tse Sum Bui, B., Wolff, M., Marquet, A., Trautwein, A.X. and Rohmer, M. Isoprenoid biosynthesis in chloroplasts via the methylerythritol phosphate pathway: the (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase (GcpE) from Arabidopsis thaliana is a [4Fe-4S] protein. J. Biol. Inorg. Chem. 10 (2005) 131–137. [DOI] [PMID: 15650872]
3.	Seemann, M., Tse Sum Bui, B., Wolff, M., Tritsch, D., Campos, N., Boronat, A., Marquet, A. and Rohmer, M. Isoprenoid biosynthesis through the methylerythritol phosphate pathway: the (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase (GcpE) is a [4Fe-4S] protein. Angew. Chem. Int. Ed. Engl. 41 (2002) 4337–4339. [DOI] [PMID: 12434382]
4.	Seemann, M., Tse Sum Bui, B., Wolff, M., Miginiac-Maslow, M. and Rohmer, M. Isoprenoid biosynthesis in plant chloroplasts via the MEP pathway: direct thylakoid/ferredoxin-dependent photoreduction of GcpE/IspG. FEBS Lett. 580 (2006) 1547–1552. [DOI] [PMID: 16480720]

[EC 1.17.7.1 created 2003 as EC 1.17.4.3, transferred 2009 to EC 1.17.7.1, modified 2014]

1.17.7.3

Accepted name:

(E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase (flavodoxin)

Reaction:

(E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + H₂O + oxidized flavodoxin = 2-C-methyl-D-erythritol 2,4-cyclodiphosphate + reduced flavodoxin

For diagram of non-mevalonate terpenoid biosynthesis, click here

Other name(s):

Systematic name:

(E)-4-hydroxy-3-methylbut-2-en-1-yl-diphosphate:oxidized flavodoxin oxidoreductase

Comments:

A bacterial iron-sulfur protein that contains a [4Fe-4S] cluster. Forms part of an alternative non-mevalonate pathway for isoprenoid biosynthesis that is found in most bacteria [2]. Plants and cyanobacteria have a similar enzyme that utilizes ferredoxin rather than flavodoxin (cf. EC 1.17.7.1).

Links to other databases:

References:

1.	Hecht, S., Eisenreich, W., Adam, P., Amslinger, S., Kis, K., Bacher, A., Arigoni, D. and Rohdich, F. Studies on the nonmevalonate pathway to terpenes: the role of the GcpE (IspG) protein. Proc. Natl. Acad. Sci. USA 98 (2001) 14837–14842. [DOI] [PMID: 11752431]
2.	Zepeck, F., Grawert, T., Kaiser, J., Schramek, N., Eisenreich, W., Bacher, A. and Rohdich, F. Biosynthesis of isoprenoids. purification and properties of IspG protein from Escherichia coli. J. Org. Chem. 70 (2005) 9168–9174. [DOI] [PMID: 16268586]
3.	Puan, K.J., Wang, H., Dairi, T., Kuzuyama, T. and Morita, C.T. fldA is an essential gene required in the 2-C-methyl-D-erythritol 4-phosphate pathway for isoprenoid biosynthesis. FEBS Lett. 579 (2005) 3802–3806. [DOI] [PMID: 15978585]

[EC 1.17.7.3 created 2014]

1.17 Acting on CH or CH₂ groups

1.17.98 With other, known, acceptors

1.17.98.1

Deleted entry:

bile-acid 7α-dehydroxylase. Now known to be catalyzed by multiple enzymes.

[EC 1.17.98.1 created 2005 as EC 1.17.1.6, transferred 2006 to EC 1.17.99.5, transferred 2014 to EC 1.17.98.1, deleted 2016]

1.17.99.5

Transferred entry:

bile-acid 7α-dehydroxylase. Now classified as EC 1.17.98.1, bile-acid 7α-dehydroxylase.

[EC 1.17.99.5 created 2005 as EC 1.17.1.6, transferred 2006 to EC 1.17.99.5, deleted 2014]

1.17.99.6

Accepted name:

epoxyqueuosine reductase

Reaction:

queuosine³⁴ in tRNA + acceptor + H₂O = epoxyqueuosine³⁴ in tRNA + reduced acceptor

For diagram of queuine biosynthesis, click here

Glossary:

queuine = base Q = 2-amino-5-({[(1S,4S,5R)-4,5-dihydroxycyclopent-2-en-1-yl]amino}methyl)-1,7-dihydropyrrolo[3,2-e]pyrimidin-4-one
epoxyqueine = base oQ

Other name(s):

oQ reductase; queG (gene name); queH (gene name)

Systematic name:

queuosine³⁴ in tRNA:acceptor oxidoreductase

Comments:

This enzyme catalyses the last step in the bacterial biosynthetic pathway to queuosine, the modified guanosine base in the wobble position in tRNAs specific for Tyr, His, Asp or Asn. Two types of enzymes are known to catalyse this activity. QueG enzymes are cobalamin-dependent, while QueH enzymes contain a [4Fe-4S] metallocluster along with an adjacent coordinated iron metal.

Links to other databases:

References:

1.	Miles, Z.D., McCarty, R.M., Molnar, G. and Bandarian, V. Discovery of epoxyqueuosine (oQ) reductase reveals parallels between halorespiration and tRNA modification. Proc. Natl. Acad. Sci. USA 108 (2011) 7368–7372. [DOI] [PMID: 21502530]
2.	Zallot, R., Ross, R., Chen, W.H., Bruner, S.D., Limbach, P.A. and De Crecy-Lagard, V. Identification of a novel epoxyqueuosine reductase family by comparative genomics. ACS Chem. Biol. 12 (2017) 844–851. [DOI] [PMID: 28128549]
3.	Li, Q., Zallot, R., MacTavish, B.S., Montoya, A., Payan, D.J., Hu, Y., Gerlt, J.A., Angerhofer, A., de Crecy-Lagard, V. and Bruner, S.D. Epoxyqueuosine reductase QueH in the biosynthetic pathway to tRNA queuosine is a unique metalloenzyme. Biochemistry 60 (2021) 3152–3161. [DOI] [PMID: 34652139]

[EC 1.17.99.6 created 2014]

*EC

1.19.6.1

Accepted name:

nitrogenase (flavodoxin)

Reaction:

4 reduced flavodoxin + N₂ + 16 ATP + 16 H₂O = 4 oxidized flavodoxin + H₂ + 2 NH₃ + 16 ADP + 16 phosphate

Systematic name:

reduced flavodoxin:dinitrogen oxidoreductase (ATP-hydrolysing)

Comments:

Requires Mg²⁺. It is composed of two components, dinitrogen reductase and dinitrogenase, that can be separated but are both required for nitrogenase activity. Dinitrogen reductase is a [4Fe-4S] protein, which, at the expense of ATP, transfers electrons from a dedicated flavodoxin to dinitrogenase. Dinitrogenase is a protein complex that contains either a molybdenum-iron cofactor, a vanadium-iron cofactor, or an iron-iron cofactor, that reduces dinitrogen in three succesive two-electron reductions from nitrogen to diimine to hydrazine to two molecules of ammonia. The reduction is initiated by formation of hydrogen. The enzyme can also reduce acetylene to ethylene (but only very slowly to ethane), azide to nitrogen and ammonia, and cyanide to methane and ammonia. In the absence of a suitable substrate, hydrogen is slowly formed. Some enzymes utilize ferredoxin rather than flavodoxin as the electron donor (see EC 1.18.6.1, nitrogenase).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 9013-04-1

References:

1.	Zumft, W.G. and Mortenson, L.E. The nitrogen-fixing complex of bacteria. Biochim. Biophys. Acta 416 (1975) 1–52. [PMID: 164247]
2.	Eady, R.R., Smith, B.E., Cook, K.A. and Postgate, J.R. Nitrogenase of Klebsiella pneumoniae. Purification and properties of the component proteins. Biochem. J. 128 (1972) 655–675. [PMID: 4344006]
3.	Deistung, J., Cannon, F.C., Cannon, M.C., Hill, S. and Thorneley, R.N. Electron transfer to nitrogenase in Klebsiella pneumoniae. nifF gene cloned and the gene product, a flavodoxin, purified. Biochem. J. 231 (1985) 743–753. [PMID: 3907625]

[EC 1.19.6.1 created 1984, modified 2014]

1.21 Acting on X-H and Y-H to form an X-Y bond

1.21.98 With other, known, acceptors

1.21.98.1

Accepted name:

cyclic dehypoxanthinyl futalosine synthase

Reaction:

dehypoxanthine futalosine + S-adenosyl-L-methionine = cyclic dehypoxanthinyl futalosine + 5′-deoxyadenosine + L-methionine

For diagram of the futalosine pathway, click here

Glossary:

dehypoxanthine futalosine = 3-{3-[(2R,3S,4R)-3,4,5-trihydroxytetrahydrofuran-2-yl]propanoyl}benzoate
cyclic dehypoxanthinyl futalosine = (2R,3S,4R)-3,4,5-trihydroxy-4′-oxo-3′,4,4′,5-tetrahydro-2’H,3H-spiro[furan-2,1′-naphthalene]-6′-carboxylate

Other name(s):

MqnC; dehypoxanthinyl futalosine cyclase

Systematic name:

dehypoxanthine futalosine:S-adenosyl-L-methionine oxidoreductase (cyclizing)

Comments:

This enzyme is a member of the ‘AdoMet radical’ (radical SAM) family. The enzyme, found in several bacterial species, is part of the futalosine pathway for menaquinone biosynthesis.

Links to other databases:

References:

1.	Hiratsuka, T., Furihata, K., Ishikawa, J., Yamashita, H., Itoh, N., Seto, H. and Dairi, T. An alternative menaquinone biosynthetic pathway operating in microorganisms. Science 321 (2008) 1670–1673. [DOI] [PMID: 18801996]
2.	Cooper, L.E., Fedoseyenko, D., Abdelwahed, S.H., Kim, S.H., Dairi, T. and Begley, T.P. In vitro reconstitution of the radical S-adenosylmethionine enzyme MqnC involved in the biosynthesis of futalosine-derived menaquinone. Biochemistry 52 (2013) 4592–4594. [DOI] [PMID: 23763543]

[EC 1.21.98.1 created 2014 as EC 1.21.99.2, transferred 2014 to EC 1.21.98.1]

1.21.99.2

Transferred entry:

EC 1.21.99.2, cyclic dehypoxanthinyl futalosine synthase. Now classified as EC 1.21.98.1, cyclic dehypoxanthinyl futalosine synthase.

[EC 1.21.99.2 created 2014, deleted 2014]

*EC

2.1.1.192

Accepted name:

23S rRNA (adenine²⁵⁰³-C²)-methyltransferase

Reaction:

(1) 2 S-adenosyl-L-methionine + adenine²⁵⁰³ in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5′-deoxyadenosine + 2-methyladenine²⁵⁰³ in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
(2) 2 S-adenosyl-L-methionine + adenine³⁷ in tRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5′-deoxyadenosine + 2-methyladenine³⁷ in tRNA + 2 oxidized [2Fe-2S] ferredoxin

Other name(s):

RlmN; YfgB; Cfr

Systematic name:

S-adenosyl-L-methionine:23S rRNA (adenine²⁵⁰³-C²)-methyltransferase

Comments:

Contains an [4Fe-4S] cluster [2]. This enzyme is a member of the ’AdoMet radical’ (radical SAM) family. S-Adenosyl-L-methionine acts as both a radical generator and as the source of the appended methyl group. RlmN first transfers an CH₂ group to a conserved cysteine (Cys³⁵⁵ in Escherichia coli) [6], the generated radical from a second S-adenosyl-L-methionine then attacks the methyl group, exctracting a hydrogen. The formed radical forms a covalent intermediate with the adenine group of the tRNA [9]. RlmN is an endogenous enzyme used by the cell to refine functions of the ribosome in protein synthesis [2]. The enzyme methylates adenosine by a radical mechanism with CH₂ from the S-adenosyl-L-methionine and retention of the hydrogen at C-2 of adenosine²⁵⁰³ of 23S rRNA. It will also methylate 8-methyladenosine²⁵⁰³ of 23S rRNA. cf. EC 2.1.1.224 [23S rRNA (adenine²⁵⁰³-C⁸)-methyltransferase].

Links to other databases:

References:

1.	Toh, S.M., Xiong, L., Bae, T. and Mankin, A.S. The methyltransferase YfgB/RlmN is responsible for modification of adenosine 2503 in 23S rRNA. RNA 14 (2008) 98–106. [DOI] [PMID: 18025251]
2.	Yan, F., LaMarre, J.M., Röhrich, R., Wiesner, J., Jomaa, H., Mankin, A.S. and Fujimori, D.G. RlmN and Cfr are radical SAM enzymes involved in methylation of ribosomal RNA. J. Am. Chem. Soc. 132 (2010) 3953–3964. [DOI] [PMID: 20184321]
3.	Yan, F. and Fujimori, D.G. RNA methylation by radical SAM enzymes RlmN and Cfr proceeds via methylene transfer and hydride shift. Proc. Natl. Acad. Sci. USA 108 (2011) 3930–3934. [DOI] [PMID: 21368151]
4.	Grove, T.L., Benner, J.S., Radle, M.I., Ahlum, J.H., Landgraf, B.J., Krebs, C. and Booker, S.J. A radically different mechanism for S-adenosylmethionine-dependent methyltransferases. Science 332 (2011) 604–607. [DOI] [PMID: 21415317]
5.	Boal, A.K., Grove, T.L., McLaughlin, M.I., Yennawar, N.H., Booker, S.J. and Rosenzweig, A.C. Structural basis for methyl transfer by a radical SAM enzyme. Science 332 (2011) 1089–1092. [DOI] [PMID: 21527678]
6.	Grove, T.L., Radle, M.I., Krebs, C. and Booker, S.J. Cfr and RlmN contain a single [4Fe-4S] cluster, which directs two distinct reactivities for S-adenosylmethionine: methyl transfer by S_N2 displacement and radical generation. J. Am. Chem. Soc. 133 (2011) 19586–19589. [DOI] [PMID: 21916495]
7.	McCusker, K.P., Medzihradszky, K.F., Shiver, A.L., Nichols, R.J., Yan, F., Maltby, D.A., Gross, C.A. and Fujimori, D.G. Covalent intermediate in the catalytic mechanism of the radical S-adenosyl-L-methionine methyl synthase RlmN trapped by mutagenesis. J. Am. Chem. Soc. 134 (2012) 18074–18081. [DOI] [PMID: 23088750]
8.	Benitez-Paez, A., Villarroya, M. and Armengod, M.E. The Escherichia coli RlmN methyltransferase is a dual-specificity enzyme that modifies both rRNA and tRNA and controls translational accuracy. RNA 18 (2012) 1783–1795. [DOI] [PMID: 22891362]
9.	Silakov, A., Grove, T.L., Radle, M.I., Bauerle, M.R., Green, M.T., Rosenzweig, A.C., Boal, A.K. and Booker, S.J. Characterization of a cross-linked protein-nucleic acid substrate radical in the reaction catalyzed by RlmN. J. Am. Chem. Soc. 136 (2014) 8221–8228. [DOI] [PMID: 24806349]

[EC 2.1.1.192 created 2010, modified 2011, modified 2014]

*EC

2.1.1.224

Accepted name:

23S rRNA (adenine²⁵⁰³-C⁸)-methyltransferase

Reaction:

2 S-adenosyl-L-methionine + adenine²⁵⁰³ in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5′-deoxyadenosine + 8-methyladenine²⁵⁰³ in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin

Other name(s):

Cfr (gene name)

Systematic name:

S-adenosyl-L-methionine:23S rRNA (adenine²⁵⁰³-C⁸)-methyltransferase

Comments:

This enzyme is a member of the ’AdoMet radical’ (radical SAM) family. S-Adenosyl-L-methionine acts as both a radical generator and as the source of the appended methyl group. It contains an [4Fe-4S] cluster [3,6,7]. Cfr is an plasmid-acquired methyltransferase that protects cells from the action of antibiotics [1]. The enzyme methylates adenosine at position 2503 of 23S rRNA by a radical mechanism, transferring a CH₂ group from S-adenosyl-L-methionine while retaining the hydrogen at the C-8 position of the adenine. Cfr first transfers an CH₂ group to a conserved cysteine (Cys³³⁸ in Staphylococcus aureus) [7], the generated radical from a second S-adenosyl-L-methionine then attacks the methyl group, exctracting a hydrogen. The formed radical forms a covalent intermediate with the adenine group of the tRNA [8]. The enzyme will also methylate 2-methyladenine produced by the action of EC 2.1.1.192 [23S rRNA (adenine²⁵⁰³-C²)-methyltransferase].

Links to other databases:

References:

1.	Giessing, A.M., Jensen, S.S., Rasmussen, A., Hansen, L.H., Gondela, A., Long, K., Vester, B. and Kirpekar, F. Identification of 8-methyladenosine as the modification catalyzed by the radical SAM methyltransferase Cfr that confers antibiotic resistance in bacteria. RNA 15 (2009) 327–336. [DOI] [PMID: 19144912]
2.	Kaminska, K.H., Purta, E., Hansen, L.H., Bujnicki, J.M., Vester, B. and Long, K.S. Insights into the structure, function and evolution of the radical-SAM 23S rRNA methyltransferase Cfr that confers antibiotic resistance in bacteria. Nucleic Acids Res. 38 (2010) 1652–1663. [DOI] [PMID: 20007606]
3.	Yan, F., LaMarre, J.M., Röhrich, R., Wiesner, J., Jomaa, H., Mankin, A.S. and Fujimori, D.G. RlmN and Cfr are radical SAM enzymes involved in methylation of ribosomal RNA. J. Am. Chem. Soc. 132 (2010) 3953–3964. [DOI] [PMID: 20184321]
4.	Yan, F. and Fujimori, D.G. RNA methylation by radical SAM enzymes RlmN and Cfr proceeds via methylene transfer and hydride shift. Proc. Natl. Acad. Sci. USA 108 (2011) 3930–3934. [DOI] [PMID: 21368151]
5.	Grove, T.L., Benner, J.S., Radle, M.I., Ahlum, J.H., Landgraf, B.J., Krebs, C. and Booker, S.J. A radically different mechanism for S-adenosylmethionine-dependent methyltransferases. Science 332 (2011) 604–607. [DOI] [PMID: 21415317]
6.	Boal, A.K., Grove, T.L., McLaughlin, M.I., Yennawar, N.H., Booker, S.J. and Rosenzweig, A.C. Structural basis for methyl transfer by a radical SAM enzyme. Science 332 (2011) 1089–1092. [DOI] [PMID: 21527678]
7.	Grove, T.L., Radle, M.I., Krebs, C. and Booker, S.J. Cfr and RlmN contain a single [4Fe-4S] cluster, which directs two distinct reactivities for S-adenosylmethionine: methyl transfer by S_N2 displacement and radical generation. J. Am. Chem. Soc. 133 (2011) 19586–19589. [DOI] [PMID: 21916495]
8.	Grove, T.L., Livada, J., Schwalm, E.L., Green, M.T., Booker, S.J. and Silakov, A. A substrate radical intermediate in catalysis by the antibiotic resistance protein Cfr. Nat. Chem. Biol. 9 (2013) 422–427. [DOI] [PMID: 23644479]

[EC 2.1.1.224 created 2011, modified 2014]

2.1.1.308

Accepted name:

cytidylyl-2-hydroxyethylphosphonate methyltransferase

Reaction:

2 S-adenosyl-L-methionine + cytidine 5′-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} + reduced acceptor = S-adenosyl-L-homocysteine + 5′-deoxyadenosine + L-methionine + cytidine 5′-({hydroxy[(S)-2-hydroxypropyl]phosphonoyl}phosphate) + oxidized acceptor (overall reaction)
(1a) S-adenosyl-L-methionine + cob(I)alamin = S-adenosyl-L-homocysteine + methylcob(III)alamin
(1b) methylcob(III)alamin + cytidine 5′-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} + S-adenosyl-L-methionine = cob(III)alamin + cytidine 5′-({hydroxy[(S)-2-hydroxypropyl]phosphonoyl}phosphate) + 5′-deoxyadenosine + L-methionine
(1c) cob(III)alamin + reduced acceptor = cob(I)alamin + oxidized acceptor

Other name(s):

Fom3; S-adenosyl-L-methionine:methylcob(III)alamin:2-hydroxyethylphosphonate methyltransferase (incorrect); 2-hydroxyethylphosphonate methyltransferase (incorrect); S-adenosyl-L-methionine:cytidine 5′-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} C-methyltransferase

Systematic name:

S-adenosyl-L-methionine:cytidine 5′-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} C²-methyltransferase

Comments:

Requires cobalamin. The enzyme, isolated from the bacterium Streptomyces wedmorensis, is involved in fosfomycin biosynthesis. It is a radical S-adenosyl-L-methionine (SAM) enzyme that contains a [4Fe-4S] center and a methylcob(III)alamin cofactor. The enzyme uses two molecues of SAM for the reaction. One molecule forms a 5′-deoxyadenosyl radical, while the other is used to methylate the cobalamin cofactor. The 5′-deoxyadenosyl radical abstracts a hydrogen from the C₂ position of cytidine 5′-{[(2-hydroxyethyl)phosphonoyl]phosphate} forming a free radical that reacts with the methyl group on methylcob(III)alamin at the opposite side from SAM and the [4Fe-4S] cluster with inversion of configuration to produce the (S)-isomer of the methylated product and cob(III)alamin. Both the [4Fe-4S] cluster and the cob(III)alamin need to be reduced by an unknown factor(s) before the enzyme could catalyse another cycle.

Links to other databases:

References:

1.	Woodyer, R.D., Li, G., Zhao, H. and van der Donk, W.A. New insight into the mechanism of methyl transfer during the biosynthesis of fosfomycin. Chem. Commun. (Camb.) (2007) 359–361. [DOI] [PMID: 17220970]
2.	Allen, K.D. and Wang, S.C. Initial characterization of Fom3 from Streptomyces wedmorensis: The methyltransferase in fosfomycin biosynthesis. Arch. Biochem. Biophys. 543 (2014) 67–73. [DOI] [PMID: 24370735]
3.	Sato, S., Kudo, F., Kim, S.Y., Kuzuyama, T. and Eguchi, T. Methylcobalamin-dependent radical SAM C-methyltransferase Fom3 recognizes cytidylyl-2-hydroxyethylphosphonate and catalyzes the nonstereoselective C-methylation in fosfomycin biosynthesis. Biochemistry 56 (2017) 3519–3522. [DOI] [PMID: 28678474]
4.	Blaszczyk, A.J. and Booker, S.J. A (re)discovery of the Fom3 substrate. Biochemistry 57 (2018) 891–892. [DOI] [PMID: 29345912]
5.	Sato, S., Kudo, F., Kuzuyama, T., Hammerschmidt, F. and Eguchi, T. C-methylation catalyzed by Fom3, a cobalamin-dependent radical S-adenosyl-L-methionine enzyme in fosfomycin biosynthesis, proceeds with inversion of configuration. Biochemistry 57 (2018) 4963–4966. [DOI] [PMID: 29966085]

[EC 2.1.1.308 created 2014, modified 2019, modified 2024]

2.1.1.309

Accepted name:

18S rRNA (guanine¹⁵⁷⁵-N⁷)-methyltransferase

Reaction:

S-adenosyl-L-methionine + guanine¹⁵⁷⁵ in 18S rRNA = S-adenosyl-L-homocysteine + N⁷-methylguanine¹⁵⁷⁵ in 18S rRNA

Other name(s):

18S rRNA methylase Bud23; BUD23 (gene name)

Systematic name:

S-adenosyl-L-methionine:18S rRNA (guanine¹⁵⁷⁵-N⁷)-methyltransferase

Comments:

The enzyme, found in eukaryotes, is involved in pre-rRNA processing. The numbering corresponds to the enzyme from the yeast Saccharomyces cerevisiae [1].

Links to other databases:

References:

1.	White, J., Li, Z., Sardana, R., Bujnicki, J.M., Marcotte, E.M. and Johnson, A.W. Bud23 methylates G¹⁵⁷⁵ of 18S rRNA and is required for efficient nuclear export of pre-40S subunits. Mol. Cell Biol. 28 (2008) 3151–3161. [DOI] [PMID: 18332120]

[EC 2.1.1.309 created 2014]

2.1.1.310

Accepted name:

25S rRNA (cytosine²⁸⁷⁰-C⁵)-methyltransferase

Reaction:

S-adenosyl-L-methionine + cytosine²⁸⁷⁰ in 25S rRNA = S-adenosyl-L-homocysteine + 5-methylcytosine²⁸⁷⁰ in 25S rRNA

Other name(s):

NOP2 (gene name)

Systematic name:

S-adenosyl-L-methionine:25S rRNA (cytosine²⁸⁷⁰-C⁵)-methyltransferase

Comments:

The enzyme, found in eukaryotes, is specific for cytosine²⁸⁷⁰ of the 25S ribosomal RNA. The numbering corresponds to the enzyme from the yeast Saccharomyces cerevisiae [1].

Links to other databases:

References:

1.	Sharma, S., Yang, J., Watzinger, P., Kotter, P. and Entian, K.D. Yeast Nop2 and Rcm1 methylate C²⁸⁷⁰ and C²²⁷⁸ of the 25S rRNA, respectively. Nucleic Acids Res. 41 (2013) 9062–9076. [DOI] [PMID: 23913415]

[EC 2.1.1.310 created 2014]

2.1.1.311

Accepted name:

25S rRNA (cytosine²²⁷⁸-C⁵)-methyltransferase

Reaction:

S-adenosyl-L-methionine + cytosine²²⁷⁸ in 25S rRNA = S-adenosyl-L-homocysteine + 5-methylcytosine²²⁷⁸ in 25S rRNA

Other name(s):

RCM1 (gene name)

Systematic name:

S-adenosyl-L-methionine:25S rRNA (cytosine²²⁷⁸-C⁵)-methyltransferase

Comments:

The enzyme, found in eukaryotes, is specific for 25S cytosine²²⁷⁸. The numbering corresponds to the enzyme from the yeast Saccharomyces cerevisiae [1].

Links to other databases:

References:

1.	Sharma, S., Yang, J., Watzinger, P., Kotter, P. and Entian, K.D. Yeast Nop2 and Rcm1 methylate C²⁸⁷⁰ and C²²⁷⁸ of the 25S rRNA, respectively. Nucleic Acids Res. 41 (2013) 9062–9076. [DOI] [PMID: 23913415]

[EC 2.1.1.311 created 2014]

2.1.1.312

Accepted name:

25S rRNA (uracil²⁸⁴³-N³)-methyltransferase

Reaction:

S-adenosyl-L-methionine + uracil²⁸⁴³ in 25S rRNA = S-adenosyl-L-homocysteine + N³-methyluracil²⁸⁴³ in 25S rRNA

Other name(s):

BMT6

Systematic name:

S-adenosyl-L-methionine:tRNA (uracil²⁸⁴³-N³)-methyltransferase

Comments:

The enzyme, described from the yeast Saccharomyces cerevisiae, is involved in ribosome biogenesis.

Links to other databases:

References:

1.	Sharma, S., Yang, J., Duttmann, S., Watzinger, P., Kotter, P. and Entian, K.D. Identification of novel methyltransferases, Bmt5 and Bmt6, responsible for the m³U methylations of 25S rRNA in Saccharomyces cerevisiae. Nucleic Acids Res. 42 (2014) 3246–3260. [DOI] [PMID: 24335083]

[EC 2.1.1.312 created 2014]

2.1.1.313

Accepted name:

25S rRNA (uracil²⁶³⁴-N³)-methyltransferase

Reaction:

S-adenosyl-L-methionine + uracil²⁶³⁴ in 25S rRNA = S-adenosyl-L-homocysteine + N³-methyluracil²⁶³⁴ in 25S rRNA

Other name(s):

BMT5

Systematic name:

S-adenosyl-L-methionine:tRNA (uracil²⁶³⁴-N³)-methyltransferase

Comments:

The enzyme, described from the yeast Saccharomyces cerevisiae, is involved in ribosome biogenesis.

Links to other databases:

References:

1.	Sharma, S., Yang, J., Duttmann, S., Watzinger, P., Kotter, P. and Entian, K.D. Identification of novel methyltransferases, Bmt5 and Bmt6, responsible for the m³U methylations of 25S rRNA in Saccharomyces cerevisiae. Nucleic Acids Res. 42 (2014) 3246–3260. [DOI] [PMID: 24335083]

[EC 2.1.1.313 created 2014]

2.2.1.12

Accepted name:

3-acetyloctanal synthase

Reaction:

pyruvate + (E)-oct-2-enal = (S)-3-acetyloctanal + CO₂

Other name(s):

pigD (gene name)

Systematic name:

pyruvate:(E)-oct-2-enal acetaldehydetransferase (decarboxylating)

Comments:

Requires thiamine diphosphate. The enzyme, characterized from the bacterium Serratia marcescens, participates in the biosynthesis of the antibiotic prodigiosin. The enzyme decarboxylates pyruvate, followed by attack of the resulting two-carbon fragment on (E)-oct-2-enal, resulting in a Stetter reaction. In vitro the enzyme can act on a number of α,β-unsaturated carbonyl compounds, including aldehydes and ketones, and can catalyse both 1-2 and 1-4 carboligations depending on the substrate.

Links to other databases:

References:

1.	Williamson, N.R., Simonsen, H.T., Ahmed, R.A., Goldet, G., Slater, H., Woodley, L., Leeper, F.J. and Salmond, G.P. Biosynthesis of the red antibiotic, prodigiosin, in Serratia: identification of a novel 2-methyl-3-n-amyl-pyrrole (MAP) assembly pathway, definition of the terminal condensing enzyme, and implications for undecylprodigiosin biosynthesis in Streptomyces. Mol. Microbiol. 56 (2005) 971–989. [DOI] [PMID: 15853884]
2.	Dresen, C., Richter, M., Pohl, M., Ludeke, S. and Müller, M. The enzymatic asymmetric conjugate umpolung reaction. Angew. Chem. Int. Ed. Engl. 49 (2010) 6600–6603. [DOI] [PMID: 20669204]
3.	Kasparyan, E., Richter, M., Dresen, C., Walter, L.S., Fuchs, G., Leeper, F.J., Wacker, T., Andrade, S.L., Kolter, G., Pohl, M. and Müller, M. Asymmetric Stetter reactions catalyzed by thiamine diphosphate-dependent enzymes. Appl. Microbiol. Biotechnol. 98 (2014) 9681–9690. [DOI] [PMID: 24957249]

[EC 2.2.1.12 created 2014]

2.3.1.234

Accepted name:

N⁶-L-threonylcarbamoyladenine synthase

Reaction:

L-threonylcarbamoyladenylate + adenine³⁷ in tRNA = AMP + N⁶-L-threonylcarbamoyladenine³⁷ in tRNA

For diagram of N⁶-L-Threonylcarbamoyladenosine³⁷ modified tRNA biosynthesis, click here

Glossary:

N⁶-L-threonylcarbamoyladenine³⁷ = t⁶A₃₇

Other name(s):

t6A synthase; Kae1; ygjD (gene name); Qri7

Systematic name:

L-threonylcarbamoyladenylate:adenine³⁷ in tRNA N⁶-L-threonylcarbamoyltransferase

Comments:

The enzyme is involved in the synthesis of N⁶-threonylcarbamoyladenosine³⁷ in tRNAs, which is found in tRNAs with the anticodon NNU, i.e. tRNA^Ile, tRNA^Thr, tRNA^Asn, tRNA^Lys, tRNA^Ser and tRNA^Arg [3].

Links to other databases:

References:

1.	Lauhon, C.T. Mechanism of N⁶-threonylcarbamoyladenonsine (t⁶A) biosynthesis: isolation and characterization of the intermediate threonylcarbamoyl-AMP. Biochemistry 51 (2012) 8950–8963. [DOI] [PMID: 23072323]
2.	Deutsch, C., El Yacoubi, B., de Crecy-Lagard, V. and Iwata-Reuyl, D. Biosynthesis of threonylcarbamoyl adenosine (t⁶A), a universal tRNA nucleoside. J. Biol. Chem. 287 (2012) 13666–13673. [DOI] [PMID: 22378793]
3.	Perrochia, L., Crozat, E., Hecker, A., Zhang, W., Bareille, J., Collinet, B., van Tilbeurgh, H., Forterre, P. and Basta, T. In vitro biosynthesis of a universal t⁶A tRNA modification in Archaea and Eukarya. Nucleic Acids Res. 41 (2013) 1953–1964. [DOI] [PMID: 23258706]
4.	Wan, L.C.K., Mao, D.Y.L., Neculai, D., Strecker, J., Chiovitti, D., Kurinov, I., Poda, G., Thevakumaran, N., Yuan, F., Szilard, R.K., Lissina, E., Nislow, C., Caudy, A.A., Durocher, D. and Sicheri, F. Reconstitution and characterization of eukaryotic N⁶-threonylcarbamoylation of tRNA using a minimal enzyme system. Nucleic Acids Res. 41 (2013) 6332–6346. [DOI] [PMID: 23620299]

[EC 2.3.1.234 created 2014 as EC 2.6.99.4, transferred 2014 to EC 2.3.1.234]

2.3.1.235

Accepted name:

tetracenomycin F2 synthase

Reaction:

10 malonyl-CoA = tetracenomycin F2 + 10 CoA + 10 CO₂ + 2 H₂O

For diagram of polyketides biosynthesis, click here

Glossary:

tetracenomycin F2 = 4-(3-acetyl-4,5,7,10-tetrahydroxyanthracen-2-yl)-3-oxobutanoic acid

Other name(s):

TCM PKS

Systematic name:

malonyl-CoA:acetate malonyltransferase (tetracenomycin-F2-forming)

Comments:

A multi-domain polyketide synthase involved in the synthesis of tetracenomycin in the bacterium Streptomyces glaucescens. It involves a ketosynthase complex (TcmKL), an acyl carrier protein (TcmM), a malonyl CoA:ACP acyltransferase (MAT), and a cyclase (TcmN). A malonyl-CoA molecule is initially bound to the acyl carrier protein and decarboxylated to form an acetyl starter unit. Additional two-carbon units are added from nine more malonyl-CoA molecules.

Links to other databases:

References:

1.	Bao, W., Wendt-Pienkowski, E. and Hutchinson, C.R. Reconstitution of the iterative type II polyketide synthase for tetracenomycin F2 biosynthesis. Biochemistry 37 (1998) 8132–8138. [DOI] [PMID: 9609708]

[EC 2.3.1.235 created 2014]

2.3.1.236

Accepted name:

5-methylnaphthoic acid synthase

Reaction:

acetyl-CoA + 5 malonyl-CoA + 3 NADPH + 3 H⁺ = 5-methyl-1-naphthoate + 6 CoA + 5 CO₂ + 4 H₂O + 3 NADP⁺

For diagram of polyketides biosynthesis, click here

Other name(s):

AziB

Systematic name:

malonyl-CoA:acetyl-CoA malonyltransferase (5-methyl-1-naphthoic acid-forming)

Comments:

A multi-domain polyketide synthase involved in the synthesis of azinomycin B in the bacterium Streptomyces griseofuscus.

Links to other databases:

References:

Zhao, Q., He, Q., Ding, W., Tang, M., Kang, Q., Yu, Y., Deng, W., Zhang, Q., Fang, J., Tang, G. and Liu, W. Characterization of the azinomycin B biosynthetic gene cluster revealing a different iterative type I polyketide synthase for naphthoate biosynthesis. Chem. Biol. 15 (2008) 693–705. [DOI] [PMID: 18635006]

[EC 2.3.1.236 created 2014]

2.3.1.237

Accepted name:

neocarzinostatin naphthoate synthase

Reaction:

acetyl-CoA + 5 malonyl-CoA + 2 NADPH + 2 H⁺ = 2-hydroxy-5-methyl-1-naphthoate + 6 CoA + 5 CO₂ + 3 H₂O + 2 NADP⁺

For diagram of polyketides biosynthesis, click here

Other name(s):

naphthoic acid synthase; NNS; ncsB (gene name)

Systematic name:

malonyl-CoA:acetyl-CoA malonyltransferase (2-hydroxy-5-methyl-1-naphthoic acid-forming)

Comments:

A multi-domain polyketide synthase involved in the synthesis of neocarzinostatin in the bacterium Streptomyces carzinostaticus.

Links to other databases:

References:

1.	Sthapit, B., Oh, T.J., Lamichhane, R., Liou, K., Lee, H.C., Kim, C.G. and Sohng, J.K. Neocarzinostatin naphthoate synthase: an unique iterative type I PKS from neocarzinostatin producer Streptomyces carzinostaticus. FEBS Lett. 566 (2004) 201–206. [DOI] [PMID: 15147895]

[EC 2.3.1.237 created 2014]

2.3.1.238

Accepted name:

monacolin J acid methylbutanoate transferase

Reaction:

monacolin J acid + (S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase] = lovastatin acid + [2-methylbutanoate polyketide synthase]

For diagram of lovastatin biosynthesis, click here

Glossary:

monacolin J acid = (3R,5R)-7-[(1S,2S,6R,8S,8aR)-8-hydroxy-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoate
lovastatin acid = (3R,5R)-7-[(1S,2S,6R,8S,8aR)-2,6-dimethyl-8-{[(2S)-2-methylbutanoyl]oxy}-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoate

Other name(s):

LovD

Systematic name:

monacolin J acid:(S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase] (S)-2-methylbutanoate transferase

Comments:

The enzyme catalyses the ultimate reaction in the lovastatin biosynthesis pathway of the filamentous fungus Aspergillus terreus.

Links to other databases:

References:

1.	Kennedy, J., Auclair, K., Kendrew, S.G., Park, C., Vederas, J.C. and Hutchinson, C.R. Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. Science 284 (1999) 1368–1372. [DOI] [PMID: 10334994]
2.	Xie, X., Watanabe, K., Wojcicki, W.A., Wang, C.C. and Tang, Y. Biosynthesis of lovastatin analogs with a broadly specific acyltransferase. Chem. Biol. 13 (2006) 1161–1169. [DOI] [PMID: 17113998]
3.	Xie, X., Meehan, M.J., Xu, W., Dorrestein, P.C. and Tang, Y. Acyltransferase mediated polyketide release from a fungal megasynthase. J. Am. Chem. Soc. 131 (2009) 8388–8389. [DOI] [PMID: 19530726]

[EC 2.3.1.238 created 2014]

2.3.1.239

Accepted name:

10-deoxymethynolide synthase

Reaction:

malonyl-CoA + 5 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H⁺ = 10-deoxymethynolide + 6 CoA + 6 CO₂ + 5 NADP⁺ + 2 H₂O

For diagram of methymycin and pikromycin biosynthesis, click here

Other name(s):

pikromycin PKS

Systematic name:

(2S)-methylmalonyl-CoA:malonyl-CoA malonyltransferase (10-deoxymethynolide-forming)

Comments:

The product, 10-deoxymethynolide, contains a 12-membered ring and is an intermediate in the biosynthesis of methymycin in the bacterium Streptomyces venezuelae. The enzyme also produces narbonolide (see EC 2.3.1.240, narbonolide synthase). The enzyme has 29 active sites arranged in four polypeptides (pikAI - pikAIV) with a loading domain, six extension modules and a terminal thioesterase domain. Each extension module contains a ketosynthase (KS), keto reductase (KR), an acyltransferase (AT) and an acyl-carrier protein (ACP). Not all active sites are used in the biosynthesis.

Links to other databases:

References:

1.	Lu, H., Tsai, S.C., Khosla, C. and Cane, D.E. Expression, site-directed mutagenesis, and steady state kinetic analysis of the terminal thioesterase domain of the methymycin/picromycin polyketide synthase. Biochemistry 41 (2002) 12590–12597. [DOI] [PMID: 12379101]
2.	Kittendorf, J.D., Beck, B.J., Buchholz, T.J., Seufert, W. and Sherman, D.H. Interrogating the molecular basis for multiple macrolactone ring formation by the pikromycin polyketide synthase. Chem. Biol. 14 (2007) 944–954. [DOI] [PMID: 17719493]
3.	Yan, J., Gupta, S., Sherman, D.H. and Reynolds, K.A. Functional dissection of a multimodular polypeptide of the pikromycin polyketide synthase into monomodules by using a matched pair of heterologous docking domains. ChemBioChem 10 (2009) 1537–1543. [DOI] [PMID: 19437523]
4.	Whicher, J.R., Dutta, S., Hansen, D.A., Hale, W.A., Chemler, J.A., Dosey, A.M., Narayan, A.R., Hakansson, K., Sherman, D.H., Smith, J.L. and Skiniotis, G. Structural rearrangements of a polyketide synthase module during its catalytic cycle. Nature 510 (2014) 560–564. [DOI] [PMID: 24965656]

[EC 2.3.1.239 created 2014]

2.3.1.240

Accepted name:

narbonolide synthase

Reaction:

malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H⁺ = narbonolide + 7 CoA + 7 CO₂ + 5 NADP⁺ + 2 H₂O

For diagram of methymycin and pikromycin biosynthesis, click here

Other name(s):

pikromycin PKS

Systematic name:

(2S)-methylmalonyl-CoA:malonyl-CoA malonyltransferase (narbonolide-forming)

Comments:

The product, narbonolide, contains a 14-membered ring and is an intermediate in the biosynthesis of narbonomycin and pikromycin in the bacterium Streptomyces venezuelae. The enzyme also produces 10-deoxymethynolide (see EC 2.3.1.239, 10-deoxymethynolide synthase). The enzyme has 29 active sites arranged in four polypeptides (pikAI - pikAIV) with a loading domain, six extension modules and a terminal thioesterase domain. Each extension module contains a ketosynthase (KS), keto reductase (KR), an acyltransferase (AT) and an acyl-carrier protein (ACP). Not all active sites are used in the biosynthesis.

Links to other databases:

References:

1.	Lu, H., Tsai, S.C., Khosla, C. and Cane, D.E. Expression, site-directed mutagenesis, and steady state kinetic analysis of the terminal thioesterase domain of the methymycin/picromycin polyketide synthase. Biochemistry 41 (2002) 12590–12597. [DOI] [PMID: 12379101]
2.	Kittendorf, J.D., Beck, B.J., Buchholz, T.J., Seufert, W. and Sherman, D.H. Interrogating the molecular basis for multiple macrolactone ring formation by the pikromycin polyketide synthase. Chem. Biol. 14 (2007) 944–954. [DOI] [PMID: 17719493]
3.	Yan, J., Gupta, S., Sherman, D.H. and Reynolds, K.A. Functional dissection of a multimodular polypeptide of the pikromycin polyketide synthase into monomodules by using a matched pair of heterologous docking domains. ChemBioChem 10 (2009) 1537–1543. [DOI] [PMID: 19437523]
4.	Whicher, J.R., Dutta, S., Hansen, D.A., Hale, W.A., Chemler, J.A., Dosey, A.M., Narayan, A.R., Hakansson, K., Sherman, D.H., Smith, J.L. and Skiniotis, G. Structural rearrangements of a polyketide synthase module during its catalytic cycle. Nature 510 (2014) 560–564. [DOI] [PMID: 24965656]

[EC 2.3.1.240 created 2014]

2.3.1.241

Accepted name:

Kdo₂-lipid IV_A acyltransferase

Reaction:

a fatty acyl-[acyl-carrier protein] + an α-Kdo-(2→4)-α-Kdo-(2→6)-[lipid IV_A] = an α-Kdo-(2→4)-α-Kdo-(2→6)-(acyl)-[lipid IV_A] + an [acyl-carrier protein]

For diagram of Kdo-Kdo-Lipid IV_A metabolism, click here

Glossary:

Other name(s):

LpxL; htrB (gene name); dodecanoyl-[acyl-carrier protein]:α-Kdo-(2→4)-α-Kdo-(2→6)-lipid IV_A O-dodecanoyltransferase; lauroyl-[acyl-carrier protein]:Kdo₂-lipid IV_A O-lauroyltransferase; (Kdo)₂-lipid IV_A lauroyltransferase; α-Kdo-(2→4)-α-(2→6)-lipid IV_A lauroyltransferase; dodecanoyl-[acyl-carrier protein]:Kdo₂-lipid IV_A O-dodecanoyltransferase; Kdo₂-lipid IV_A lauroyltransferase

Systematic name:

fatty acyl-[acyl-carrier protein]:α-Kdo-(2→4)-α-Kdo-(2→6)-[lipid IV_A] O-acyltransferase

Comments:

The enzyme is involved in the biosynthesis of the phosphorylated outer membrane glycolipid lipid A. It transfers an acyl group to the 3-O position of the 3R-hydroxyacyl already attached to the nitrogen of the non-reducing glucosamine molecule. The enzyme from the bacterium Escherichia coli is specific for lauryl (C₁₂) acyl groups, giving the enzyme its previous accepted name. However, enzymes from different species accept highly variable substrates.

Links to other databases:

References:

1.	Clementz, T., Bednarski, J.J. and Raetz, C.R. Function of the htrB high temperature requirement gene of Escherichia coli in the acylation of lipid A: HtrB catalyzed incorporation of laurate. J. Biol. Chem. 271 (1996) 12095–12102. [DOI] [PMID: 8662613]
2.	van der Ley, P., Steeghs, L., Hamstra, H.J., ten Hove, J., Zomer, B. and van Alphen, L. Modification of lipid A biosynthesis in Neisseria meningitidis lpxL mutants: influence on lipopolysaccharide structure, toxicity, and adjuvant activity. Infect. Immun. 69 (2001) 5981–5990. [DOI] [PMID: 11553534]
3.	McLendon, M.K., Schilling, B., Hunt, J.R., Apicella, M.A. and Gibson, B.W. Identification of LpxL, a late acyltransferase of Francisella tularensis. Infect. Immun. 75 (2007) 5518–5531. [DOI] [PMID: 17724076]
4.	Six, D.A., Carty, S.M., Guan, Z. and Raetz, C.R. Purification and mutagenesis of LpxL, the lauroyltransferase of Escherichia coli lipid A biosynthesis. Biochemistry 47 (2008) 8623–8637. [DOI] [PMID: 18656959]
5.	Fathy Mohamed, Y., Hamad, M., Ortega, X.P. and Valvano, M.A. The LpxL acyltransferase is required for normal growth and penta-acylation of lipid A in Burkholderia cenocepacia. Mol. Microbiol. 104 (2017) 144–162. [DOI] [PMID: 28085228]

[EC 2.3.1.241 created 2014, modified 2021]

2.3.1.242

Accepted name:

Kdo₂-lipid IV_A palmitoleoyltransferase

Reaction:

a (9Z)-hexadec-9-enoyl-[acyl-carrier protein] + Kdo₂-lipid IV_A = (9Z)-hexadec-9-enoyl-Kdo₂-lipid IV_A + an [acyl-carrier protein]

For diagram of Kdo-Kdo-Lipid IV_A metabolism, click here

Glossary:

Kdo = 3-deoxy-D-manno-oct-2-ulopyranosylonic acid
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-glucopyranosyl phosphate
Kdo₂-lipid IV_A = α-Kdo-(2→4)-α-Kdo-(2→6)-lipid IV_A
(9Z)-hexadec-9-enoyl = palmitoleoyl
(9Z)-hexadec-9-enoyl-Kdo₂-lipid IV_A = α-Kdo-(2→4)-α-Kdo-(2→6)-2-deoxy-2-{(3R)-3-[(9Z)-hexadec-9-enoyl]tetradecanamido}-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-glucopyranosyl phosphate

Other name(s):

LpxP; palmitoleoyl-acyl carrier protein-dependent acyltransferase; cold-induced palmitoleoyl transferase; palmitoleoyl-[acyl-carrier protein]:Kdo₂-lipid IV_A O-palmitoleoyltransferase; (Kdo)₂-lipid IV_A palmitoleoyltransferase; α-Kdo-(2→4)-α-(2→6)-lipid IV_A palmitoleoyltransferase

Systematic name:

(9Z)-hexadec-9-enoyl-[acyl-carrier protein]:Kdo₂-lipid IV_A O-palmitoleoyltransferase

Comments:

The enzyme, characterized from the bacterium Escherichia coli, is induced upon cold shock and is involved in the formation of a cold-adapted variant of the outer membrane glycolipid lipid A.

Links to other databases:

References:

1.	Carty, S.M., Sreekumar, K.R. and Raetz, C.R. Effect of cold shock on lipid A biosynthesis in Escherichia coli. Induction At 12 degrees C of an acyltransferase specific for palmitoleoyl-acyl carrier protein. J. Biol. Chem. 274 (1999) 9677–9685. [DOI] [PMID: 10092655]
2.	Vorachek-Warren, M.K., Carty, S.M., Lin, S., Cotter, R.J. and Raetz, C.R. An Escherichia coli mutant lacking the cold shock-induced palmitoleoyltransferase of lipid A biosynthesis: absence of unsaturated acyl chains and antibiotic hypersensitivity at 12 degrees C. J. Biol. Chem. 277 (2002) 14186–14193. [DOI] [PMID: 11830594]

[EC 2.3.1.242 created 2014]

2.3.1.243

Accepted name:

acyl-Kdo₂-lipid IV_A acyltransferase

Reaction:

a fatty acyl-[acyl-carrier protein] + an α-Kdo-(2→4)-α-Kdo-(2→6)-(acyl)-[lipid IV_A] = an α-Kdo-(2→4)-α-Kdo-(2→6)-(acyl)₂-[lipid IV_A] + an [acyl-carrier protein]

For diagram of Kdo-Kdo-Lipid IV_A metabolism, click here

Glossary:

Kdo = 3-deoxy-D-manno-oct-2-ulopyranosylonic acid
a lipid IV_A = 2-deoxy-2-{[(3R)-3-hydroxyacyl]amino}-3-O-[(3R)-3-hydroxyacyl]-4-O-phospho-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxyacyl]-2-{[(3R)-3-hydroxyacyl]amino}-1-O-phospho-α-D-glucopyranose
an α-Kdo-(2→4)-α-Kdo-(2→6)-(acyl)-[lipid IV_A] = 3-deoxy-α-D-manno-oct-2-ulopyranosyl-(2→4)-3-deoxy-α-D-manno-oct-2-ulopyranosyl-(2→6)-2-deoxy-2-{[(3R)-3-(acyloxy)acyl]amino}-3-O-[(3R)-3-hydroxyacyl]-4-O-phospho-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxyacyl]-2-{[(3R)-3-hydroxyacyl]amino}-1-O-phosphono-α-D-glucopyranose
an α-Kdo-(2→4)-α-Kdo-(2→6)-(acyl)₂-[lipid IV_A] = 3-deoxy-α-D-manno-oct-2-ulopyranosyl-(2→4)-3-deoxy-α-D-manno-oct-2-ulopyranosyl-(2→6)-2-deoxy-2-{[(3R)-3-(acyloxy)acyl]amino}-3-O-[(3R)-3-(acyloxy)acyl]-4-O-phospho-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxyacyl]-2-{[(3R)-3-hydroxyacyl]amino}-1-O-phospho-α-D-glucopyranose

Other name(s):

lpxM (gene name); MsbB acyltransferase; myristoyl-[acyl-carrier protein]:α-Kdo-(2→4)-α-Kdo-(2→6)-(dodecanoyl)-lipid IV_A O-myristoyltransferase; tetradecanoyl-[acyl-carrier protein]:dodecanoyl-Kdo₂-lipid IV_A O-tetradecanoyltransferase; lauroyl-Kdo₂-lipid IV_A myristoyltransferase

Systematic name:

fatty acyl-[acyl-carrier protein]:α-Kdo-(2→4)-α-Kdo-(2→6)-(acyl)-[lipid IV_A] O-acyltransferase

Comments:

The enzyme is involved in the biosynthesis of the phosphorylated outer membrane glycolipid lipid A. It transfers an acyl group to the 3-O position of the 3R-hydroxyacyl already attached at the 2-O position of the non-reducing glucosamine molecule. The enzyme from the bacterium Escherichia coli is specific for myristoyl (C₁₄) acyl groups, giving the enzyme its previous accepted name. However, enzymes from different species accept highly variable substrates.

Links to other databases:

References:

1.	Clementz, T., Zhou, Z. and Raetz, C.R. Function of the Escherichia coli msbB gene, a multicopy suppressor of htrB knockouts, in the acylation of lipid A. Acylation by MsbB follows laurate incorporation by HtrB. J. Biol. Chem. 272 (1997) 10353–10360. [DOI] [PMID: 9099672]
2.	Dovala, D., Rath, C.M., Hu, Q., Sawyer, W.S., Shia, S., Elling, R.A., Knapp, M.S. and Metzger, L.E., 4th. Structure-guided enzymology of the lipid A acyltransferase LpxM reveals a dual activity mechanism. Proc. Natl. Acad. Sci. USA 113 (2016) E6064–E6071. [DOI] [PMID: 27681620]

[EC 2.3.1.243 created 2014, modified 2021]

2.4.1.332

Accepted name:

1,2-α-glucosylglycerol phosphorylase

Reaction:

2-O-α-D-glucopyranosyl-glycerol + phosphate = β-D-glucose 1-phosphate + glycerol

Other name(s):

2-O-α-D-glucopyranosylglycerol phosphorylase

Systematic name:

2-O-α-D-glucopyranosyl-glycerol:phosphate β-D-glucosyltransferase

Comments:

The enzyme has been isolated from the bacterium Bacillus selenitireducens. In the absence of glycerol the enzyme produces α-D-glucopyranose and phosphate from β-D-glucopyranose 1-phosphate. In this reaction the glucosyl residue is transferred to a water molecule with an inversion of the anomeric conformation.

Links to other databases:

References:

1.	Nihira, T., Saito, Y., Ohtsubo, K., Nakai, H. and Kitaoka, M. 2-O-α-D-glucosylglycerol phosphorylase from Bacillus selenitireducens MLS10 possessing hydrolytic activity on β-D-glucose 1-phosphate. PLoS One 9:e86548 (2014). [DOI] [PMID: 24466148]
2.	Touhara, K.K., Nihira, T., Kitaoka, M., Nakai, H. and Fushinobu, S. Structural basis for reversible phosphorolysis and hydrolysis reactions of 2-O-α-glucosylglycerol phosphorylase. J. Biol. Chem. 289 (2014) 18067–18075. [DOI] [PMID: 24828502]

[EC 2.4.1.332 created 2014]

2.4.1.333

Accepted name:

1,2-β-oligoglucan phosphorylase

Reaction:

[(1→2)-β-D-glucosyl]_n + phosphate = [(1→2)-β-D-glucosyl]_n-1 + α-D-glucose 1-phosphate

Systematic name:

1,2-β-D-glucan:phosphate α-D-glucosyltransferase

Comments:

The enzyme has been isolated from the bacterium Listeria innocua. It catalyses the reversible phosphorolysis of β-(1→2)-D-glucans. The minimum length of the substrate for the phosphorolytic reaction is 3 D-glucose units. In the synthetic reaction starting from sophorose and α-D-glucose 1-phosphate the average polymerisation degree is 39.

Links to other databases:

References:

1.	Nakajima, M., Toyoizumi, H., Abe, K., Nakai, H., Taguchi, H. and Kitaoka, M. 1,2-β-Oligoglucan phosphorylase from Listeria innocua. PLoS One 9:e92353 (2014). [DOI] [PMID: 24647662]

[EC 2.4.1.333 created 2014]

2.4.1.334

Accepted name:

1,3-α-oligoglucan phosphorylase

Reaction:

[(1→3)-α-D-glucosyl]_n + phosphate = [(1→3)-α-D-glucosyl]_n-1 + β-D-glucose 1-phosphate

Systematic name:

1,3-α-D-glucan:phosphate β-D-glucosyltransferase

Comments:

The enzyme, isolated from the bacterium Clostridium phytofermentans, catalyses a reversible reaction. Substrates for the phosphorolytic reaction are α-1,3-linked oligoglucans with a polymerisation degree of 3 or more. Nigerose (i.e. 3-O-α-D-glucopyranosyl-D-glucopyranose) is not phosphorylyzed but can serve as substrate in the reverse direction (cf. EC 2.4.1.279, nigerose phosphorylase).

Links to other databases:

References:

1.	Nihira, T., Nishimoto, M., Nakai, H., Ohtsubo, K., and Kitaoka, M. Characterization of two phosphorylases for α-1,3-oligoglucans from Clostridium phytofermentans. J. Appl. Glycosci. 61 (2014) 59–66.

[EC 2.4.1.334 created 2014]

*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]

*EC

2.5.1.25

Accepted name:

tRNA-uridine aminocarboxypropyltransferase

Reaction:

S-adenosyl-L-methionine + a uridine in tRNA = S-methyl-5′-thioadenosine + a 3-[(3S)-3-amino-3-carboxypropyl]uridine in tRNA

Other name(s):

S-adenosyl-L-methionine:tRNA-uridine 3-(3-amino-3-carboxypropyl)transferase; tapT (gene name); DTWD1 (gene name); DTWD2 (gene name); S-adenosyl-L-methionine:uridine⁴⁷ in tRNA^Phe 3-[(3S)-3-amino-3-carboxypropyl]transferase

Systematic name:

S-adenosyl-L-methionine:uridine in tRNA 3-[(3S)-3-amino-3-carboxypropyl]transferase

Comments:

3-[(3S)-3-amino-3-carboxypropyl]uridine (acp3U) is a highly conserved modification found in tRNA core region in bacteria and eukaryotes that confers thermal stability on tRNA. The enzyme from the bacterium Escherichia coli catalyses the modification of uridine⁴⁷ in the V-loop of tRNAs for Arg², Ile¹, Ile², Ile²v, Lys, Met, Phe, Val²A, and Val²B. The human homologs DTWD1 and DTWD2 are responsible for acp3U formation at positions 20 and 20a, respectively, in the D-loop of several cytoplasmic tRNAs.

Links to other databases:

References:

1.	Nishimura, S., Taya, Y., Kuchino, Y. and Ohashi, Z. Enzymatic synthesis of 3-(3-amino-3-carboxypropyl)uridine in Escherichia coli phenylalanine transfer RNA: transfer of the 3-amino-acid-3-carboxypropyl group from S-adenosylmethionine. Biochem. Biophys. Res. Commun. 57 (1974) 702–708. [DOI] [PMID: 4597321]
2.	Takakura, M., Ishiguro, K., Akichika, S., Miyauchi, K. and Suzuki, T. Biogenesis and functions of aminocarboxypropyluridine in tRNA. Nat. Commun. 10:5542 (2019). [DOI] [PMID: 31804502]
3.	Meyer, B., Immer, C., Kaiser, S., Sharma, S., Yang, J., Watzinger, P., Weiss, L., Kotter, A., Helm, M., Seitz, H.M., Kotter, P., Kellner, S., Entian, K.D. and Wohnert, J. Identification of the 3-amino-3-carboxypropyl (acp) transferase enzyme responsible for acp3U formation at position 47 in Escherichia coli tRNAs. Nucleic Acids Res. 48 (2020) 1435–1450. [DOI] [PMID: 31863583]

[EC 2.5.1.25 created 1984, modified 2014, modified 2020]

2.5.1.128

Accepted name:

N⁴-bis(aminopropyl)spermidine synthase

Reaction:

2 S-adenosyl 3-(methylsulfanyl)propylamine + spermidine = 2 S-methyl-5′-thioadenosine + N⁴-bis(aminopropyl)spermidine (overall reaction)
(1a) S-adenosyl 3-(methylsulfanyl)propylamine + spermidine = S-methyl-5′-thioadenosine + N⁴-aminopropylspermidine
(1b) S-adenosyl 3-(methylsulfanyl)propylamine + N⁴-aminopropylspermidine = S-methyl-5′-thioadenosine + N⁴-bis(aminopropyl)spermidine

Glossary:

spermidine = N-(3-aminopropyl)butane-1,4-diamine
N⁴-aminopropylspermidine = N,N′-bis(3-aminopropyl)butane-1,4-diamine
N⁴-bis(aminopropyl)spermidine = N,N,N′-tris(3-aminopropyl)butane-1,4-diamine

Systematic name:

S-adenosyl 3-(methylsulfanyl)propylamine:spermidine 3-aminopropyltransferase [N⁴-bis(aminopropyl)spermidine synthesizing]

Comments:

The enzyme, characterized from the thermophilic archaeon Thermococcus kodakarensis, synthesizes the branched-chain polyamine N⁴-bis(aminopropyl)spermidine, which is required for cell growth at high-temperature. When spermine is used as substrate, the enzyme forms N⁴-aminopropylspermine.

Links to other databases:

References:

Okada, K., Hidese, R., Fukuda, W., Niitsu, M., Takao, K., Horai, Y., Umezawa, N., Higuchi, T., Oshima, T., Yoshikawa, Y., Imanaka, T. and Fujiwara, S. Identification of a novel aminopropyltransferase involved in the synthesis of branched-chain polyamines in hyperthermophiles. J. Bacteriol. 196 (2014) 1866–1876. [DOI] [PMID: 24610711]

[EC 2.5.1.128 created 2014]

2.6.99.4

Transferred entry:

N⁶-L-threonylcarbamoyladenine synthase. Now EC 2.3.1.234, N⁶-L-threonylcarbamoyladenine synthase.

[EC 2.6.99.4 created 2014, deleted 2014]

*EC

2.7.7.67

Accepted name:

CDP-2,3-bis-(O-geranylgeranyl)-sn-glycerol synthase

Reaction:

CTP + 2,3-bis-(O-geranylgeranyl)-sn-glycerol 1-phosphate = diphosphate + CDP-2,3-bis-(O-geranylgeranyl)-sn-glycerol

For diagram of archaetidylserine biosynthesis, click here

Glossary:

2,3-bis-(O-geranylgeranyl)-sn-glycerol 1-phosphate = 2,3-bis-(O-geranylgeranyl)-glycerophosphate ether = unsaturated archaetidic acid
CDP-unsaturated archaeol = CDP-2,3-bis-(O-geranylgeranyl)-sn-glycerol

Other name(s):

carS (gene name); CDP-2,3-di-O-geranylgeranyl-sn-glycerol synthase; CTP:2,3-GG-GP ether cytidylyltransferase; CTP:2,3-di-O-geranylgeranyl-sn-glycero-1-phosphate cytidyltransferase; CDP-2,3-bis-O-(geranylgeranyl)-sn-glycerol synthase; CTP:2,3-bis-O-(geranylgeranyl)-sn-glycero-1-phosphate cytidylyltransferase; CDP-unsaturated archaeol synthase; CDP-archaeol synthase (incorrect)

Systematic name:

CTP:2,3-bis-(O-geranylgeranyl)-sn-glycerol 1-phosphate cytidylyltransferase

Comments:

This enzyme catalyses one of the steps in the biosynthesis of polar lipids in archaea, which are characterized by having an sn-glycerol 1-phosphate backbone rather than an sn-glycerol 3-phosphate backbone as is found in bacteria and eukaryotes [1]. The enzyme requires Mg²⁺ and K⁺ for maximal activity [1].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 329791-09-5

References:

1.	Morii, H., Nishihara, M. and Koga, Y. CTP:2,3-di-O-geranylgeranyl-sn-glycero-1-phosphate cytidyltransferase in the methanogenic archaeon Methanothermobacter thermoautotrophicus. J. Biol. Chem. 275 (2000) 36568–36574. [DOI] [PMID: 10960477]
2.	Morii, H. and Koga, Y. CDP-2,3-di-O-geranylgeranyl-sn-glycerol:L-serine O-archaetidyltransferase (archaetidylserine synthase) in the methanogenic archaeon Methanothermobacter thermautotrophicus. J. Bacteriol. 185 (2003) 1181–1189. [DOI] [PMID: 12562787]
3.	Jain, S., Caforio, A., Fodran, P., Lolkema, J.S., Minnaard, A.J. and Driessen, A.J. Identification of CDP-archaeol synthase, a missing link of ether lipid biosynthesis in Archaea. Chem. Biol. 21 (2014) 1392–1401. [DOI] [PMID: 25219966]

[EC 2.7.7.67 created 2009, modified 2014]

2.7.8.41

Accepted name:

cardiolipin synthase (CMP-forming)

Reaction:

a CDP-diacylglycerol + a phosphatidylglycerol = a cardiolipin + CMP

Systematic name:

CDP-diacylglycerol:phosphatidylglycerol diacylglycerolphosphotransferase (CMP-forming)

Comments:

The eukaryotic enzyme is involved in the biosynthesis of the mitochondrial phospholipid cardiolipin. It requires divalent cations for activity.

Links to other databases:

References:

1.	Schlame, M. and Hostetler, K.Y. Solubilization, purification, and characterization of cardiolipin synthase from rat liver mitochondria. Demonstration of its phospholipid requirement. J. Biol. Chem. 266 (1991) 22398–22403. [PMID: 1657995]
2.	Nowicki, M., Muller, F. and Frentzen, M. Cardiolipin synthase of Arabidopsis thaliana. FEBS Lett. 579 (2005) 2161–2165. [DOI] [PMID: 15811335]
3.	Houtkooper, R.H., Akbari, H., van Lenthe, H., Kulik, W., Wanders, R.J., Frentzen, M. and Vaz, F.M. Identification and characterization of human cardiolipin synthase. FEBS Lett. 580 (2006) 3059–3064. [DOI] [PMID: 16678169]
4.	Sandoval-Calderon, M., Geiger, O., Guan, Z., Barona-Gomez, F. and Sohlenkamp, C. A eukaryote-like cardiolipin synthase is present in Streptomyces coelicolor and in most actinobacteria. J. Biol. Chem. 284 (2009) 17383–17390. [DOI] [PMID: 19439403]

[EC 2.7.8.41 created 2014]

*EC

2.8.1.6

Accepted name:

biotin synthase

Reaction:

dethiobiotin + sulfur-(sulfur carrier) + 2 S-adenosyl-L-methionine + 2 reduced [2Fe-2S] ferredoxin = biotin + (sulfur carrier) + 2 L-methionine + 2 5′-deoxyadenosine + 2 oxidized [2Fe-2S] ferredoxin

Glossary:

biotin = 5[(3aS,4S,6aR)-2-oxohexahydro(4H-thieno[4,5-d]imidazol-4-yl)]pentanoate
4,5-secobiotin = 6-[(4R,5R)-2-oxo-5-(sulfanylmethyl)imidazolidin-4-yl]hexanoate = 9-mercaptodethiobiotin

Other name(s):

dethiobiotin:sulfur sulfurtransferase

Systematic name:

dethiobiotin:sulfur-(sulfur carrier) sulfurtransferase

Comments:

The enzyme binds a [4Fe-4S] and a [2Fe-2S] cluster. In every reaction cycle, the enzyme consumes two molecules of AdoMet. The first reaction produces 5′-deoxyadenosine and 4,5-secobiotin. Reaction with another equivalent of AdoMet results in abstraction of the C-6 methylene pro-S hydrogen atom from 4,5-secobiotin, and the resulting carbon radical is quenched via formation of an intramolecular C-S bond, thus closing the biotin tetrahydrothiophene ring. The sulfur donor is believed to be the [2Fe-2S] cluster, which is sacrificed in the process, so that in vitro the reaction is a single turnover. In vivo, the [2Fe-2S] cluster can be reassembled by the Isc or Suf iron-sulfur cluster assembly systems, to allow further catalysis.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 80146-93-6

References:

1.	Trainor, D.A., Parry, R.J. and Gitterman, A. Biotin biosynthesis. 2. Stereochemistry of sulfur introduction at C-4 of dethiobiotin. J. Am. Chem. Soc. 102 (1980) 1467–1468.
2.	Shiuan, D. and Campbell, A. Transcriptional regulation and gene arrangement of Escherichia coli, Citrobacter freundii and Salmonella typhimurium biotin operons. Gene 67 (1988) 203–211. [DOI] [PMID: 2971595]
3.	Zhang, S., Sanyal, I., Bulboaca, G.H., Rich, A. and Flint, D.H. The gene for biotin synthase from Saccharomyces cerevisiae: cloning, sequencing, and complementation of Escherichia coli strains lacking biotin synthase. Arch. Biochem. Biophys. 309 (1994) 29–35. [DOI] [PMID: 8117110]
4.	Ugulava, N.B., Gibney, B.R. and Jarrett, J.T. Biotin synthase contains two distinct iron-sulfur cluster binding sites: chemical and spectroelectrochemical analysis of iron-sulfur cluster interconversions. Biochemistry 40 (2001) 8343–8351. [DOI] [PMID: 11444981]
5.	Berkovitch, F., Nicolet, Y., Wan, J.T., Jarrett, J.T. and Drennan, C.L. Crystal structure of biotin synthase, an S-adenosylmethionine-dependent radical enzyme. Science 303 (2004) 76–79. [DOI] [PMID: 14704425]
6.	Lotierzo, M., Tse Sum Bui, B., Florentin, D., Escalettes, F. and Marquet, A. Biotin synthase mechanism: an overview. Biochem. Soc. Trans. 33 (2005) 820–823. [DOI] [PMID: 16042606]
7.	Taylor, A.M., Farrar, C.E. and Jarrett, J.T. 9-Mercaptodethiobiotin is formed as a competent catalytic intermediate by Escherichia coli biotin synthase. Biochemistry 47 (2008) 9309–9317. [DOI] [PMID: 18690713]
8.	Reyda, M.R., Fugate, C.J. and Jarrett, J.T. A complex between biotin synthase and the iron-sulfur cluster assembly chaperone HscA that enhances in vivo cluster assembly. Biochemistry 48 (2009) 10782–10792. [DOI] [PMID: 19821612]

[EC 2.8.1.6 created 1999, modified 2006, modified 2011, modified 2014]

*EC

2.8.1.8

Accepted name:

lipoyl synthase

Reaction:

[protein]-N⁶-(octanoyl)-L-lysine + an [Fe-S] cluster scaffold protein carrying a [4Fe-4S]²⁺ cluster + 2 S-adenosyl-L-methionine + 2 oxidized [2Fe-2S] ferredoxin + 6 H⁺ = [protein]-N⁶-[(R)-dihydrolipoyl]-L-lysine + an [Fe-S] cluster scaffold protein + 2 sulfide + 4 Fe³⁺ + 2 L-methionine + 2 5′-deoxyadenosine + 2 reduced [2Fe-2S] ferredoxin

Other name(s):

lipA (gene name); LS; lipoate synthase; protein 6-N-(octanoyl)lysine:sulfur sulfurtransferase; protein N⁶-(octanoyl)lysine:sulfur sulfurtransferase; protein N⁶-(octanoyl)lysine:sulfur-(sulfur carrier) sulfurtransferase

Systematic name:

[protein]-N⁶-(octanoyl)-L-lysine:an [Fe-S] cluster scaffold protein carrying a [4Fe-4S]²⁺ cluster sulfurtransferase

Comments:

This enzyme catalyses the final step in the de-novo biosynthesis of the lipoyl cofactor, the attachment of two sulfhydryl groups to C₆ and C₈ of a pendant octanoyl chain. It is a member of the ‘AdoMet radical’ (radical SAM) family, all members of which produce the 5′-deoxyadenosin-5′-yl radical and methionine from AdoMet (S-adenosylmethionine) by the addition of an electron from an iron-sulfur centre. The enzyme contains two [4Fe-4S] clusters. The first cluster produces the radicals, which are converted into 5′-deoxyadenosine when they abstract hydrogen atoms from C₆ and C₈, respectively, leaving reactive radicals at these positions that interact with sulfur atoms within the second (auxiliary) cluster. Having donated two sulfur atoms, the auxiliary cluster is degraded during catalysis, but is regenerated immediately by the transfer of a new cluster from iron-sulfur cluster carrier proteins [8]. Lipoylation is essential for the function of several key enzymes involved in oxidative metabolism, as it converts apoprotein into the biologically active holoprotein. Examples of such lipoylated proteins include pyruvate dehydrogenase (E₂ domain), 2-oxoglutarate dehydrogenase (E₂ domain), the branched-chain 2-oxoacid dehydrogenases and the glycine cleavage system (H protein) [1,2]. An alternative lipoylation pathway involves EC 6.3.1.20, lipoate—protein ligase, which can lipoylate apoproteins using exogenous lipoic acid (or its analogues) [4].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 189398-80-9

References:

1.	Cicchillo, R.M. and Booker, S.J. Mechanistic investigations of lipoic acid biosynthesis in Escherichia coli: both sulfur atoms in lipoic acid are contributed by the same lipoyl synthase polypeptide. J. Am. Chem. Soc. 127 (2005) 2860–2861. [DOI] [PMID: 15740115]
2.	Vanden Boom, T.J., Reed, K.E. and Cronan, J.E., Jr. Lipoic acid metabolism in Escherichia coli: isolation of null mutants defective in lipoic acid biosynthesis, molecular cloning and characterization of the E. coli lip locus, and identification of the lipoylated protein of the glycine cleavage system. J. Bacteriol. 173 (1991) 6411–6420. [DOI] [PMID: 1655709]
3.	Zhao, X., Miller, J.R., Jiang, Y., Marletta, M.A. and Cronan, J.E. Assembly of the covalent linkage between lipoic acid and its cognate enzymes. Chem. Biol. 10 (2003) 1293–1302. [DOI] [PMID: 14700636]
4.	Cicchillo, R.M., Iwig, D.F., Jones, A.D., Nesbitt, N.M., Baleanu-Gogonea, C., Souder, M.G., Tu, L. and Booker, S.J. Lipoyl synthase requires two equivalents of S-adenosyl-L-methionine to synthesize one equivalent of lipoic acid. Biochemistry 43 (2004) 6378–6386. [DOI] [PMID: 15157071]
5.	Jordan, S.W. and Cronan, J.E., Jr. A new metabolic link. The acyl carrier protein of lipid synthesis donates lipoic acid to the pyruvate dehydrogenase complex in Escherichia coli and mitochondria. J. Biol. Chem. 272 (1997) 17903–17906. [DOI] [PMID: 9218413]
6.	Miller, J.R., Busby, R.W., Jordan, S.W., Cheek, J., Henshaw, T.F., Ashley, G.W., Broderick, J.B., Cronan, J.E., Jr. and Marletta, M.A. Escherichia coli LipA is a lipoyl synthase: in vitro biosynthesis of lipoylated pyruvate dehydrogenase complex from octanoyl-acyl carrier protein. Biochemistry 39 (2000) 15166–15178. [DOI] [PMID: 11106496]
7.	Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annu. Rev. Biochem. 69 (2000) 961–1004. [DOI] [PMID: 10966480]
8.	McCarthy, E.L. and Booker, S.J. Destruction and reformation of an iron-sulfur cluster during catalysis by lipoyl synthase. Science 358 (2017) 373–377. [DOI] [PMID: 29051382]

[EC 2.8.1.8 created 2006, modified 2014, modified 2018]

3.1.1.97

Accepted name:

methylated diphthine methylhydrolase

Reaction:

diphthine methyl ester-[translation elongation factor 2] + H₂O = diphthine-[translation elongation factor 2] + methanol

For diagram of diphthamide biosynthesis, click here

Glossary:

diphthine methyl ester = 2-[(3S)-3-carboxy methyl ester-3-(trimethylammonio)propyl]-L-histidine
diphthine = 2-[(3S)-3-carboxy-3-(trimethylammonio)propyl]-L-histidine

Other name(s):

Dph7; diphthine methylesterase (incorrect)

Systematic name:

diphthine methyl ester acylhydrolase

Comments:

The protein is only present in eukaryotes.

Links to other databases:

References:

1.	Lin, Z., Su, X., Chen, W., Ci, B., Zhang, S. and Lin, H. Dph7 catalyzes a previously unknown demethylation step in diphthamide biosynthesis. J. Am. Chem. Soc. 136 (2014) 6179–6182. [DOI] [PMID: 24739148]

[EC 3.1.1.97 created 2014, modified 2015]

3.1.3.96

Accepted name:

pseudouridine 5′-phosphatase

Reaction:

pseudouridine 5′-phosphate + H₂O = pseudouridine + phosphate

Other name(s):

pseudouridine 5′-monophosphatase; 5′-PsiMPase; HDHD1

Systematic name:

pseudouridine 5′-phosphohydrolase

Comments:

Requires Mg²⁺ for activity.

Links to other databases:

References:

1.	Preumont, A., Rzem, R., Vertommen, D. and Van Schaftingen, E. HDHD1, which is often deleted in X-linked ichthyosis, encodes a pseudouridine-5′-phosphatase. Biochem. J. 431 (2010) 237–244. [DOI] [PMID: 20722631]

[EC 3.1.3.96 created 2014]

3.5.1.27

Deleted entry:

N-formylmethionylaminoacyl-tRNA deformylase. The activity is covered by EC 3.5.1.88, peptide deformylase

[EC 3.5.1.27 created 1972, deleted 2014]

3.5.2.20

Accepted name:

isatin hydrolase

Reaction:

isatin + H₂O = isatinate

Glossary:

isatin = 1H-indole-2,3-dione
isatinate = 2-(2-aminophenyl)-2-oxoacetate

Systematic name:

isatin amidohydrolase

Comments:

Requires Mn²⁺. This enzyme, found in several bacterial species, is involved in the degradation of indole-3-acetic acid.

Links to other databases:

References:

1.	Sommer, M.R. and Jochimsen, B. Identification of enzymes involved in indole-3-acetic acid degradation. Plant Soil 186 (1996) 143–149.
2.	Bjerregaard-Andersen, K., Sommer, T., Jensen, J.K., Jochimsen, B., Etzerodt, M. and Morth, J.P. A proton wire and water channel revealed in the crystal structure of isatin hydrolase. J. Biol. Chem. 289 (2014) 21351–21359. [DOI] [PMID: 24917679]

[EC 3.5.2.20 created 2014]

*EC

3.5.4.20

Accepted name:

pyrithiamine deaminase

Reaction:

1-(4-amino-2-methylpyrimid-5-ylmethyl)-3-(2-hydroxyethyl)-2-methylpyridinium + H₂O = 1-(4-hydroxy-2-methylpyrimid-5-ylmethyl)-3-(2-hydroxyethyl)-2-methylpyridinium + NH₃

Glossary:

pyrithiamine = 1-(4-amino-2-methylpyrimid-5-ylmethyl)-3-(2-hydroxyethyl)-2-methylpyridinium bromide hydrobromide

Other name(s):

1-(4-amino-2-methylpyrimid-5-ylmethyl)-3-(β-hydroxyethyl)-2-methylpyridinium-bromide aminohydrolase

Systematic name:

1-(4-amino-2-methylpyrimid-5-ylmethyl)-3-(2-hydroxyethyl)-2-methylpyridinium aminohydrolase

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 37289-23-9

References:

1.	Sinha, A.K. and Chatterjee, G.C. Metabolism of pyrithiamine by the pyrithiamine-requiring mutant of Staphylococcus aureus. Biochem. J. 107 (1968) 165–169. [PMID: 5641872]

[EC 3.5.4.20 created 1972, modified 2014]

3.6.1.67

Accepted name:

dihydroneopterin triphosphate diphosphatase

Reaction:

7,8-dihydroneopterin 3′-triphosphate + H₂O = 7,8-dihydroneopterin 3′-phosphate + diphosphate

Other name(s):

folQ (gene name); nudB (gene name); NUDT1 (gene name); dihydroneopterin triphosphate pyrophosphohydrolase

Systematic name:

7,8-dihydroneopterin 3′-triphosphate diphosphohydrolase

Comments:

The enzyme participates in a folate biosynthesis pathway, which is found in bacteria, fungi, and plants. Requires Mg²⁺.

Links to other databases:

References:

1.	Suzuki, Y. and Brown, G.M. The biosynthesis of folic acid. XII. Purification and properties of dihydroneopterin triphosphate pyrophosphohydrolase. J. Biol. Chem. 249 (1974) 2405–2410. [PMID: 4362677]
2.	O'Handley, S.F., Frick, D.N., Bullions, L.C., Mildvan, A.S. and Bessman, M.J. Escherichia coli orf17 codes for a nucleoside triphosphate pyrophosphohydrolase member of the MutT family of proteins. Cloning, purification, and characterization of the enzyme. J. Biol. Chem. 271 (1996) 24649–24654. [DOI] [PMID: 8798731]
3.	Klaus, S.M., Wegkamp, A., Sybesma, W., Hugenholtz, J., Gregory, J.F., 3rd and Hanson, A.D. A nudix enzyme removes pyrophosphate from dihydroneopterin triphosphate in the folate synthesis pathway of bacteria and plants. J. Biol. Chem. 280 (2005) 5274–5280. [DOI] [PMID: 15611104]
4.	Gabelli, S.B., Bianchet, M.A., Xu, W., Dunn, C.A., Niu, Z.D., Amzel, L.M. and Bessman, M.J. Structure and function of the E. coli dihydroneopterin triphosphate pyrophosphatase: a Nudix enzyme involved in folate biosynthesis. Structure 15 (2007) 1014–1022. [DOI] [PMID: 17698004]

[EC 3.6.1.67 created 2014]

*EC

4.1.99.19

Accepted name:

2-iminoacetate synthase

Reaction:

L-tyrosine + S-adenosyl-L-methionine + NADPH = 2-iminoacetate + 4-methylphenol + 5′-deoxyadenosine + L-methionine + NADP⁺ + H⁺

For diagram of thiamine diphosphate biosynthesis, click here

Glossary:

4-methylphenol = 4-cresol = p-cresol

Other name(s):

thiH (gene name)

Systematic name:

L-tyrosine 4-methylphenol-lyase (2-iminoacetate-forming)

Comments:

Binds a [4Fe-4S] cluster that is coordinated by 3 cysteines and an exchangeable S-adenosyl-L-methionine molecule. The first stage of catalysis is reduction of the S-adenosyl-L-methionine to produce methionine and a 5-deoxyadenosin-5-yl radical that is crucial for the conversion of the substrate. The reductant is assumed to be NADPH, which is provided by a flavoprotein:NADPH oxidoreductase system [4]. Part of the pathway for thiamine biosynthesis.

Links to other databases:

References:

1.	Leonardi, R., Fairhurst, S.A., Kriek, M., Lowe, D.J. and Roach, P.L. Thiamine biosynthesis in Escherichia coli: isolation and initial characterisation of the ThiGH complex. FEBS Lett. 539 (2003) 95–99. [DOI] [PMID: 12650933]
2.	Kriek, M., Martins, F., Challand, M.R., Croft, A. and Roach, P.L. Thiamine biosynthesis in Escherichia coli: identification of the intermediate and by-product derived from tyrosine. Angew. Chem. Int. Ed. Engl. 46 (2007) 9223–9226. [DOI] [PMID: 17969213]
3.	Kriek, M., Martins, F., Leonardi, R., Fairhurst, S.A., Lowe, D.J. and Roach, P.L. Thiazole synthase from Escherichia coli: an investigation of the substrates and purified proteins required for activity in vitro. J. Biol. Chem. 282 (2007) 17413–17423. [DOI] [PMID: 17403671]
4.	Challand, M.R., Martins, F.T. and Roach, P.L. Catalytic activity of the anaerobic tyrosine lyase required for thiamine biosynthesis in Escherichia coli. J. Biol. Chem. 285 (2010) 5240–5248. [DOI] [PMID: 19923213]

[EC 4.1.99.19 created 2011, modified 2014]

4.2.3.148

Accepted name:

cembrene C synthase

Reaction:

geranylgeranyl diphosphate = cembrene C + diphosphate

For diagram of cembrene and related diterpenoids, click here

Glossary:

cembrene C = (1E,5E,9E)-1,5,9-trimethyl-12-(propan-2-ylidene)cyclotetradeca-1,5,9-triene

Other name(s):

DtcycA (gene name)

Systematic name:

geranylgeranyl-diphosphate diphosphate-lyase (cembrene-C-forming)

Comments:

Requires Mg²⁺. Isolated from the bacterium Streptomyces sp. SANK 60404. This bifunctional enzyme also produces (R)-nephthenol. See EC 4.2.3.149, nephthenol synthase.

Links to other databases:

References:

1.	Meguro, A., Tomita, T., Nishiyama, M. and Kuzuyama, T. Identification and characterization of bacterial diterpene cyclases that synthesize the cembrane skeleton. ChemBioChem 14 (2013) 316–321. [DOI] [PMID: 23386483]

[EC 4.2.3.148 created 2014]

4.2.3.149

Accepted name:

nephthenol synthase

Reaction:

geranylgeranyl diphosphate + H₂O = (R)-nephthenol + diphosphate

For diagram of cembrene and related diterpenoids, click here

Glossary:

(R)-nephthenol = 2-[(1R,3E,7E,11E)-4,8,12-trimethyltetradeca-3,7,11-trien-1-yl]propan-2-ol

Other name(s):

DtcycA (gene name); DtcycB (gene name)

Systematic name:

geranylgeranyl-diphosphate diphosphate-lyase [(R)-nephthenol-forming]

Comments:

Requires Mg²⁺. Two isozymes with this activity were isolated from the bacterium Streptomyces sp. SANK 60404. The enzyme encoded by the DtcycA gene also produces cembrene C (see EC 4.2.3.148, cembrene C synthase), while the enzyme encoded by the DtcycB gene also produces (R)-cembrene A and (1S,4E,8E,12E)-2,2,5,9,13-pentamethylcyclopentadeca-4,8,12-trien-1-ol (see EC 4.2.3.150, cembrene A synthase, and EC 4.2.3.151, pentamethylcyclopentadecatrienol synthase).

Links to other databases:

References:

1.	Meguro, A., Tomita, T., Nishiyama, M. and Kuzuyama, T. Identification and characterization of bacterial diterpene cyclases that synthesize the cembrane skeleton. ChemBioChem 14 (2013) 316–321. [DOI] [PMID: 23386483]

[EC 4.2.3.149 created 2014]

4.2.3.150

Accepted name:

cembrene A synthase

Reaction:

geranylgeranyl diphosphate = (R)-cembrene A + diphosphate

For diagram of cembrene and related diterpenoids, click here

Glossary:

cembrene A = (1E,5E,9E,12R)-1,5,9-trimethyl-12-(propan-2-en-2-yl)cyclotetradeca-1,5,9-triene

Other name(s):

DtcycB (gene name)

Systematic name:

geranylgeranyl-diphosphate diphosphate-lyase [(R)-cembrene-A-forming]

Comments:

Requires Mg²⁺. Isolated from the bacterium Streptomyces sp. SANK 60404. This trifunctional enzyme, which contains a [4Fe-4S] cluster, also produces (R)-nephthenol and (1S,4E,8E,12E)-2,2,5,9,13-pentamethylcyclopentadeca-4,8,12-trien-1-ol. See EC 4.2.3.149, nephthenol synthase and EC 4.2.3.151, pentamethylcyclopentadecatrienol synthase.

Links to other databases:

References:

1.	Meguro, A., Tomita, T., Nishiyama, M. and Kuzuyama, T. Identification and characterization of bacterial diterpene cyclases that synthesize the cembrane skeleton. ChemBioChem 14 (2013) 316–321. [DOI] [PMID: 23386483]

[EC 4.2.3.150 created 2014]

4.2.3.151

Accepted name:

pentamethylcyclopentadecatrienol synthase

Reaction:

geranylgeranyl diphosphate + H₂O = (1S,4E,8E,12E)-2,2,5,9,13-pentamethylcyclopentadeca-4,8,12-trien-1-ol + diphosphate

For diagram of cembrene and related diterpenoids, click here

Other name(s):

DtcycB (gene name)

Systematic name:

geranylgeranyl-diphosphate diphosphate-lyase [(1S,4E,8E,12E)-2,2,5,9,13-pentamethylcyclopentadeca-4,8,12-trien-1-ol-forming]

Comments:

Requires Mg²⁺. Isolated from the bacterium Streptomyces sp. SANK 60404. This trifunctional enzyme, which contains a [4Fe-4S] cluster, also produces (R)-nephthenol and (R)-cembrene A. See EC 4.2.3.150, cembrene A synthase and EC 4.2.3.149, nephthenol synthase.

Links to other databases:

References:

1.	Meguro, A., Tomita, T., Nishiyama, M. and Kuzuyama, T. Identification and characterization of bacterial diterpene cyclases that synthesize the cembrane skeleton. ChemBioChem 14 (2013) 316–321. [DOI] [PMID: 23386483]

[EC 4.2.3.151 created 2014]

4.4.1.28

Accepted name:

L-cysteine desulfidase

Reaction:

L-cysteine + H₂O = sulfide + NH₃ + pyruvate (overall reaction)
(1a) L-cysteine = 2-aminoprop-2-enoate + sulfide
(1b) 2-aminoprop-2-enoate = 2-iminopropanoate (spontaneous)
(1c) 2-iminopropanoate + H₂O = pyruvate + NH₃ (spontaneous)

Other name(s):

L-cysteine desulfhydrase

Systematic name:

L-cysteine sulfide-lyase (deaminating; pyruvate-forming)

Comments:

The enzyme from the archaeon Methanocaldococcus jannaschii contains a [4Fe-4S] cluster and is specific for L-cysteine (cf. EC 4.4.1.1, cystathionine γ-lyase). It cleaves a carbon-sulfur bond releasing sulfide and the unstable enamine product 2-aminoprop-2-enoate that tautomerizes to an imine form, which undergoes a hydrolytic deamination to form pyruvate and ammonia. The same reaction can also be catalysed by some pyridoxal-phosphate proteins (cf. EC 4.4.1.1, cystathionine γ-lyase).

Links to other databases:

References:

1.	Tchong, S.I., Xu, H. and White, R.H. L-Cysteine desulfidase: an [4Fe-4S] enzyme isolated from Methanocaldococcus jannaschii that catalyzes the breakdown of L-cysteine into pyruvate, ammonia, and sulfide. Biochemistry 44 (2005) 1659–1670. [DOI] [PMID: 15683250]

[EC 4.4.1.28 created 2014]

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]

6.3.2.45

Accepted name:

UDP-N-acetylmuramate—L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate ligase

Reaction:

ATP + UDP-N-acetyl-α-D-muramate + L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate = ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate

Glossary:

meso-2,6-diaminoheptanedioate = meso-2,6-diaminopimelate

Other name(s):

murein peptide ligase; Mpl; yjfG (gene name); UDP-MurNAc:L-Ala-γ-D-Glu-meso-A2pm ligase; UDP-N-acetylmuramate:L-alanyl-γ-D-glutamyl-meso-diaminopimelate ligase

Systematic name:

UDP-N-acetylmuramate:L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate ligase2015

Comments:

The enzyme catalyses the reincorporation into peptidoglycan of the tripeptide L-alanyl-γ-D-glutamyl-2,6-meso-diaminoheptanedioate released during the maturation and constant remodeling of this bacterial cell wall polymer that occur during cell growth and division. The enzyme can also use the tetrapeptide L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioyl-D-alanine or the pentapeptide L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioyl-D-alanyl-D-alanine in vivo and in vitro. Requires Mg²⁺.

Links to other databases:

References:

1.	Mengin-Lecreulx, D., van Heijenoort, J. and Park, J.T. Identification of the mpl gene encoding UDP-N-acetylmuramate: L-alanyl-γ-D-glutamyl-meso-diaminopimelate ligase in Escherichia coli and its role in recycling of cell wall peptidoglycan. J. Bacteriol. 178 (1996) 5347–5352. [DOI] [PMID: 8808921]
2.	Herve, M., Boniface, A., Gobec, S., Blanot, D. and Mengin-Lecreulx, D. Biochemical characterization and physiological properties of Escherichia coli UDP-N-acetylmuramate:L-alanyl-γ-D-glutamyl-meso-diaminopimelate ligase. J. Bacteriol. 189 (2007) 3987–3995. [DOI] [PMID: 17384195]

[EC 6.3.2.45 created 2014]

*EC

6.3.4.14

Accepted name:

biotin carboxylase

Reaction:

ATP + [biotin carboxyl-carrier protein]-biotin-N⁶-L-lysine + hydrogencarbonate- = ADP + phosphate + [biotin carboxyl-carrier protein]-carboxybiotin-N⁶-L-lysine

Other name(s):

accC (gene name); biotin-carboxyl-carrier-protein:carbon-dioxide ligase (ADP-forming)

Systematic name:

[biotin carboxyl-carrier protein]-biotin-N⁶-L-lysine:hydrogencarbonate ligase (ADP-forming)

Comments:

This enzyme, part of an acetyl-CoA carboxylase complex, acts on a biotin carboxyl-carrier protein (BCCP) that has been biotinylated by EC 6.3.4.15, biotin—[biotin carboxyl-carrier protein] ligase. In some organisms the enzyme is part of a multi-domain polypeptide that also includes the carrier protein (e.g. mycobacteria). Yet in other organisms (e.g. mammals) this activity is included in a single polypeptide that also catalyses the transfer of the carboxyl group from biotin to acetyl-CoA (see EC 6.4.1.2, acetyl-CoA carboxylase).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9075-71-2

References:

1.	Dimroth, P., Guchhait, R.B., Stoll, E. and Lane, M.D. Enzymatic carboxylation of biotin: molecular and catalytic properties of a component enzyme of acetyl CoA carboxylase. Proc. Natl. Acad. Sci. USA 67 (1970) 1353–1360. [DOI] [PMID: 4922289]
2.	Norman, E., De Smet, K.A., Stoker, N.G., Ratledge, C., Wheeler, P.R. and Dale, J.W. Lipid synthesis in mycobacteria: characterization of the biotin carboxyl carrier protein genes from Mycobacterium leprae and M. tuberculosis. J. Bacteriol. 176 (1994) 2525–2531. [DOI] [PMID: 7909542]
3.	Janiyani, K., Bordelon, T., Waldrop, G.L. and Cronan, J.E., Jr. Function of Escherichia coli biotin carboxylase requires catalytic activity of both subunits of the homodimer. J. Biol. Chem. 276 (2001) 29864–29870. [DOI] [PMID: 11390406]
4.	Chou, C.Y., Yu, L.P. and Tong, L. Crystal structure of biotin carboxylase in complex with substrates and implications for its catalytic mechanism. J. Biol. Chem. 284 (2009) 11690–11697. [DOI] [PMID: 19213731]
5.	Broussard, T.C., Pakhomova, S., Neau, D.B., Bonnot, R. and Waldrop, G.L. Structural analysis of substrate, reaction intermediate, and product binding in Haemophilus influenzae biotin carboxylase. Biochemistry 54 (2015) 3860–3870. [DOI] [PMID: 26020841]

[EC 6.3.4.14 created 1976, modified 2014, modified 2018]

6.3.4.24

Accepted name:

tyramine—L-glutamate ligase

Reaction:

ATP + tyramine + L-glutamate = ADP + phosphate + γ-glutamyltyramine

For diagram of methanofuran biosynthesis, click here

Other name(s):

mfnD (gene name)

Systematic name:

tyramine:L-glutamate γ-ligase (ADP-forming)

Comments:

The enzyme, which has been characterized from the archaea Methanocaldococcus fervens, participates in the biosynthesis of the cofactor methanofuran. Requires a divalent cation for activity, with Mn²⁺ giving the highest activity, followed by Mg²⁺, Co²⁺, Zn²⁺, and Fe²⁺.

Links to other databases: