Proposed Changes to the Enzyme List

References:

1.	Liepins, J., Kuorelahti, S., Penttila, M. and Richard, P. Enzymes for the NADPH-dependent reduction of dihydroxyacetone and D-glyceraldehyde and L-glyceraldehyde in the mould Hypocrea jecorina. FEBS J. 273 (2006) 4229–4235. [DOI] [PMID: 16930134]
2.	Martens-Uzunova, E.S. and Schaap, P.J. An evolutionary conserved D-galacturonic acid metabolic pathway operates across filamentous fungi capable of pectin degradation. Fungal Genet. Biol. 45 (2008) 1449–1457. [DOI] [PMID: 18768163]

[EC 1.1.1.372 created 2014]

1.1.1.373

Accepted name:

sulfolactaldehyde 3-reductase

Reaction:

(2S)-2,3-dihydroxypropane-1-sulfonate + NAD⁺ = (2S)-3-sulfolactaldehyde + NADH + H⁺

For diagram of sulphoglycolysis of sulfoquinovose, click here

Glossary:

(2S)-3-sulfolactaldehyde = (2S)-2-hydroxy-3-oxopropane-1-sulfonate
(2S)-2,3-dihydroxypropane-1-sulfonic acid = (2S)-3-sulfopropanediol = (S)-DHPS

Other name(s):

yihU (gene name)

Systematic name:

(2S)-2,3-dihydroxypropane-1-sulfonate:NAD⁺ 3-oxidoreductase

Comments:

The enzyme, characterized from the bacterium Escherichia coli, is involved in the degradation pathway of sulfoquinovose, the polar headgroup of sulfolipids found in the photosynthetic membranes of all higher plants, mosses, ferns, algae, and most photosynthetic bacteria, as well as the surface layer of some archaea.

Links to other databases:

References:

1.	Denger, K., Weiss, M., Felux, A.K., Schneider, A., Mayer, C., Spiteller, D., Huhn, T., Cook, A.M. and Schleheck, D. Sulphoglycolysis in Escherichia coli K-12 closes a gap in the biogeochemical sulphur cycle. Nature 507 (2014) 114–117. [DOI] [PMID: 24463506]
2.	Sharma, M., Abayakoon, P., Lingford, J.P., Epa, R., John, A., Jin, Y., Goddard-Borger, E.D., Davies, G.J. and Williams, S.J. Dynamic structural changes accompany the production of dihydroxypropanesulfonate by sulfolactaldehyde reductase. ACS Catalysis 10 (2020) 2826–2836. [DOI]

[EC 1.1.1.373 created 2014]

1.1.3.3

Deleted entry:

malate oxidase. Now classified as EC 1.1.5.4, malate dehydrogenase (quinone).

[EC 1.1.3.3 created 1961, deleted 2014]

*EC

1.1.3.19

Accepted name:

4-hydroxymandelate oxidase (decarboxylating)

Reaction:

(S)-4-hydroxymandelate + O₂ = 4-hydroxybenzaldehyde + CO₂ + H₂O₂

Glossary:

(S)-4-hydroxymandelate = (S)-2-hydroxy-2-(4-hydroxyphenyl)acetate

Other name(s):

L-4-hydroxymandelate oxidase (decarboxylating); (S)-2-hydroxy-2-(4-hydroxyphenyl)acetate:oxygen 1-oxidoreductase; (S)-4-hydroxymandelate:oxygen 1-oxidoreductase; 4-hydroxymandelate oxidase

Systematic name:

(S)-4-hydroxymandelate:oxygen 1-oxidoreductase (decarboxylating)

Comments:

A flavoprotein (FAD), requires Mn²⁺. The enzyme from the bacterium Pseudomonas putida is involved in the degradation of mandelate.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 60976-30-9

References:

1.	Bhat, S.G. and Vaidyanathan, C.S. Purification and properties of L-4-hydroxymandelate oxidase from Pseudomonas convexa. Eur. J. Biochem. 68 (1976) 323–331. [DOI] [PMID: 976259]

[EC 1.1.3.19 created 1984, modified 2014]

1.1.3.46

Accepted name:

4-hydroxymandelate oxidase

Reaction:

(S)-4-hydroxymandelate + O₂ = 2-(4-hydroxyphenyl)-2-oxoacetate + H₂O₂

Glossary:

(S)-4-hydroxymandelate = (S)-2-hydroxy-2-(4-hydroxyphenyl)acetate
2-(4-hydroxyphenyl)-2-oxoacetate = 4-hydroxyphenylglyoxylate = (4-hydroxyphenyl)(oxo)acetate
L-(4-hydroxyphenyl)glycine = (S)-4-hydroxyphenylglycine
L-(3,5-dihydroxyphenyl)glycine = (S)-3,5-dihydroxyphenylglycine

Other name(s):

4HmO; HmO

Systematic name:

(S)-4-hydroxymandelate:oxygen 1-oxidoreductase

Comments:

A flavoprotein (FMN). The enzyme from the bacterium Amycolatopsis orientalis is involved in the biosynthesis of L-(4-hydroxyphenyl)glycine and L-(3,5-dihydroxyphenyl)glycine, two non-proteinogenic amino acids occurring in the vancomycin group of antibiotics.

Links to other databases:

References:

1.	Hubbard, B.K., Thomas, M.G. and Walsh, C.T. Biosynthesis of L-p-hydroxyphenylglycine, a non-proteinogenic amino acid constituent of peptide antibiotics. Chem. Biol. 7 (2000) 931–942. [DOI] [PMID: 11137816]
2.	Li, T.L., Choroba, O.W., Charles, E.H., Sandercock, A.M., Williams, D.H. and Spencer, J.B. Characterisation of a hydroxymandelate oxidase involved in the biosynthesis of two unusual amino acids occurring in the vancomycin group of antibiotics. Chem. Commun. (Camb.) (2001) 1752–1753. [PMID: 12240298]

[EC 1.1.3.46 created 2014]

*EC

1.2.1.27

Accepted name:

methylmalonate-semialdehyde dehydrogenase (CoA-acylating)

Reaction:

2-methyl-3-oxopropanoate + CoA + H₂O + NAD⁺ = propanoyl-CoA + HCO₃^- + NADH

For diagram of inositol catabolism, click here

Glossary:

methylmalonate semialdehyde = 2-methyl-3-oxopropanoate

Other name(s):

MSDH; MMSA dehydrogenase; iolA (gene name); methylmalonate-semialdehyde dehydrogenase (acylating)

Systematic name:

2-methyl-3-oxopropanoate:NAD⁺ 3-oxidoreductase (CoA-propanoylating)

Comments:

Also converts 3-oxopropanoate into acetyl-CoA [3]. The reaction occurs in two steps with the decarboxylation process preceding CoA-binding [3]. Bicarbonate rather than CO₂ is released as a final product [3].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 37205-49-5

References:

1.	Sokatch, J.R., Sanders, L.E. and Marshall, V.P. Oxidation of methylmalonate semialdehyde to propionyl coenzyme A in Pseudomonas aeruginosa grown on valine. J. Biol. Chem. 243 (1968) 2500–2506. [PMID: 4297649]
2.	Dubourg, H., Stines-Chaumeil, C., Didierjean, C., Talfournier, F., Rahuel-Clermont, S., Branlant, G. and Aubry, A. Expression, purification, crystallization and preliminary X-ray diffraction data of methylmalonate-semialdehyde dehydrogenase from Bacillus subtilis. Acta Crystallogr. D Biol. Crystallogr. 60 (2004) 1435–1437. [DOI] [PMID: 15272169]
3.	Stines-Chaumeil, C., Talfournier, F. and Branlant, G. Mechanistic characterization of the MSDH (methylmalonate semialdehyde dehydrogenase) from Bacillus subtilis. Biochem. J. 395 (2006) 107–115. [DOI] [PMID: 16332250]

[EC 1.2.1.27 created 1972, modified 2014]

*EC

1.3.1.10

Accepted name:

enoyl-[acyl-carrier-protein] reductase (NADPH, Si-specific)

Reaction:

an acyl-[acyl-carrier protein] + NADP⁺ = a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADPH + H⁺

Other name(s):

acyl-ACP dehydrogenase (ambiguous); enoyl-[acyl carrier protein] (reduced nicotinamide adenine dinucleotide phosphate) reductase; NADPH 2-enoyl Co A reductase; enoyl acyl-carrier-protein reductase (ambiguous); enoyl-ACP reductase (ambiguous); acyl-[acyl-carrier-protein]:NADP⁺ oxidoreductase (B-specific); acyl-[acyl-carrier protein]:NADP⁺ oxidoreductase (B-specific); enoyl-[acyl-carrier-protein] reductase (NADPH, B-specific)

Systematic name:

acyl-[acyl-carrier protein]:NADP⁺ oxidoreductase (Si-specific)

Comments:

One of the activities of EC 2.3.1.86, fatty-acyl-CoA synthase system, an enzyme found in yeasts (Ascomycota and Basidiomycota). Catalyses the reduction of enoyl-acyl-[acyl-carrier protein] derivatives of carbon chain length from 4 to 16. The yeast enzyme is Si-specific with respect to NADP⁺. cf. EC 1.3.1.39, enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific) and EC 1.3.1.104, enoyl-[acyl-carrier-protein] reductase (NADPH), which describes enzymes whose stereo-specificity towards NADPH is not known. See also EC 1.3.1.9, enoyl-[acyl-carrier-protein] reductase (NADH).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 37251-09-5

References:

1.	Seyama, T., Kasama, T., Yamakawa, T., Kawaguchi, A., Saito, K. and Okuda, S. Origin of hydrogen atoms in the fatty acids synthesized with yeast fatty acid synthetase. J. Biochem. (Tokyo) 82 (1977) 1325–1329. [PMID: 338601]

[EC 1.3.1.10 created 1972, modified 1986, modified 2013, modified 2014, modified 2018]

1.3.99.36

Accepted name:

cypemycin cysteine dehydrogenase (decarboxylating)

Reaction:

cypemycin(1-18)-L-Cys-L-Leu-L-Val-L-Cys + acceptor = C^3.19,S²¹-cyclocypemycin(1-18)-L-Ala-L-Leu-N-thioethenyl-L-valinamide + CO₂ + H₂S + reduced acceptor

For diagram of reaction, click here

Other name(s):

cypemycin decarboxylase; CypD

Systematic name:

cypemycin(1-18)-L-Cys-L-Leu-L-Val-L-Cys:acceptor oxidoreductase (decarboxylating, cyclizing)

Comments:

Cypemycin, isolated from the bacterium Streptomyces sp. OH-4156, is a peptide antibiotic, member of the linaridins, a class of posttranslationally modified ribosomally synthesized peptides. The enzyme decarboxylates and reduces the C-terminal L-cysteine residue, producing a reactive ethenethiol group that reacts with a dethiolated cysteine upstream to form an aminovinyl-methyl-cysteine loop that is important for the antibiotic activity of the mature peptide.

Links to other databases:

References:

1.	Claesen, J. and Bibb, M. Genome mining and genetic analysis of cypemycin biosynthesis reveal an unusual class of posttranslationally modified peptides. Proc. Natl. Acad. Sci. USA 107 (2010) 16297–16302. [DOI] [PMID: 20805503]

[EC 1.3.99.36 created 2014]

1.5.1.48

Accepted name:

2-methyl-1-pyrroline reductase

Reaction:

(R)-2-methylpyrrolidine + NADP⁺ = 2-methyl-1-pyrroline + NADPH + H⁺

Other name(s):

(R)-imine reductase (ambiguous)

Systematic name:

(R)-2-methylpyrrolidine:NADP⁺ 2-oxidoreductase

Comments:

The enzyme from the bacterium Streptomyces sp. GF3587 is highly specific for its substrate and forms only the (R) isomer.

Links to other databases:

References:

1.	Mitsukura, K., Suzuki, M., Shinoda, S., Kuramoto, T., Yoshida, T. and Nagasawa, T. Purification and characterization of a novel (R)-imine reductase from Streptomyces sp. GF3587. Biosci. Biotechnol. Biochem. 75 (2011) 1778–1782. [DOI] [PMID: 21897027]

[EC 1.5.1.48 created 2014]

*EC

1.5.4.1

Accepted name:

pyrimidodiazepine synthase

Reaction:

2-amino-6-acetyl-3,7,8,9-tetrahydro-3H-pyrimido[4,5-b][1,4]diazepin-4-one + glutathione disulfide + H₂O = 6-pyruvoyltetrahydropterin + 2 glutathione

For diagram of 6-pyruvyltetrahydropterin metabolism, click here

Glossary:

2-amino-6-acetyl-3,7,8,9-tetrahydro-3H-pyrimido[4,5-b][1,4]diazepin-4-one = pyrimidodiazepine

Other name(s):

PDA synthase; pyrimidodiazepine:oxidized-glutathione oxidoreductase (ring-opening, cyclizing); pyrimidodiazepine:glutathione-disulfide oxidoreductase (ring-opening, cyclizing)

Systematic name:

2-amino-6-acetyl-3,7,8,9-tetrahydro-3H-pyrimido[4,5-b][1,4]diazepin-4-one:glutathione-disulfide oxidoreductase (ring-opening, cyclizing)

Comments:

In the reverse direction, the reduction of 6-pyruvoyl-tetrahydropterin is accompanied by the opening of the 6-membered pyrazine ring and the formation of the 7-membered diazepine ring. The pyrimidodiazepine formed is an acetyldihydro derivative. Involved in the formation of the eye pigment drosopterin in Drosophila melanogaster.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 93586-06-2

References:

1.	Wiederrecht, G.J. and Brown, G.M. Purification and properties of the enzymes from Drosophila melanogaster that catalyze the conversion of dihydroneopterin triphosphate to the pyrimidodiazepine precursor of the drosopterins. J. Biol. Chem. 259 (1984) 14121–14127. [PMID: 6438092]
2.	Kim, J., Suh, H., Kim, S., Kim, K., Ahn, C. and Yim, J. Identification and characteristics of the structural gene for the Drosophila eye colour mutant sepia, encoding PDA synthase, a member of the ω class glutathione S-transferases. Biochem. J. 398 (2006) 451–460. [DOI] [PMID: 16712527]

[EC 1.5.4.1 created 1990, modified 2014]

*EC

1.10.3.10

Transferred entry:

ubiquinol oxidase (H⁺-transporting). Now EC 7.1.1.3, ubiquinol oxidase (H⁺-transporting)

[EC 1.10.3.10 created 2011, modified 2014, deleted 2018]

1.10.3.15

Accepted name:

grixazone synthase

Reaction:

2 3-amino-4-hydroxybenzoate + N-acetyl-L-cysteine + 2 O₂ = grixazone B + 4 H₂O + CO₂

For diagram of grixazone biosynthesis, click here

Glossary:

grixazone B = 8-amino-9-(N-acetyl-L-cystein-S-yl)-7-oxo-7H-phenoxazine-2-carboxylic acid

Other name(s):

GriF

Systematic name:

3-amino-4-hydroxybenzoate:N-acetyl-L-cysteine:oxygen oxidoreductase

Comments:

A type 3 multi copper protein. The enzyme, isolated from the bacterium Streptomyces griseus, catalyses an 8 electron oxidation. Activation of the enzyme requires a copper chaperone (GriE). It also acts on 3-amino-4-hydroxybenzaldehyde, giving grixazone A. The second aldehyde group is presumably lost as formate. The enzyme also catalyses the reaction of EC 1.10.3.4 o-aminophenol oxidase.

Links to other databases:

References:

1.	Suzuki, H., Ohnishi, Y., Furusho, Y., Sakuda, S. and Horinouchi, S. Novel benzene ring biosynthesis from C₃ and C₄ primary metabolites by two enzymes. J. Biol. Chem. 281 (2006) 36944–36951. [DOI] [PMID: 17003031]
2.	Le Roes-Hill, M., Goodwin, C. and Burton, S. Phenoxazinone synthase: what’s in a name. Trends Biotechnol. 27 (2009) 248–258. [DOI] [PMID: 19268377]

[EC 1.10.3.15 created 2014]

1.11.1.23

Accepted name:

(S)-2-hydroxypropylphosphonic acid epoxidase

Reaction:

(S)-2-hydroxypropylphosphonate + H₂O₂ = (1R,2S)-1,2-epoxypropylphosphonate + 2 H₂O

For diagram of fosfomycin biosynthesis, click here

Glossary:

(1R,2S)-1,2-epoxypropylphosphonate = fosfomycin = [(2R,3S)-3-methyloxiran-2-yl]phosphonate

Other name(s):

HPP epoxidase; HppE; 2-hydroxypropylphosphonic acid epoxidase; Fom4; (S)-2-hydroxypropylphosphonate epoxidase

Systematic name:

(S)-2-hydroxypropylphosphonate:hydrogen-peroxide epoxidase

Comments:

This is the last enzyme in the biosynthetic pathway of fosfomycin, a broad-spectrum antibiotic produced by certain Streptomyces species. Contains non heme iron that forms a iron(IV)-oxo (ferryl) complex with hydrogen peroxide, which functions as a proton abstractor from the substrate [7].

Links to other databases:

References:

1.	Munos, J.W., Moon, S.J., Mansoorabadi, S.O., Chang, W., Hong, L., Yan, F., Liu, A. and Liu, H.W. Purification and characterization of the epoxidase catalyzing the formation of fosfomycin from Pseudomonas syringae. Biochemistry 47 (2008) 8726–8735. [DOI] [PMID: 18656958]
2.	Yan, F., Moon, S.J., Liu, P., Zhao, Z., Lipscomb, J.D., Liu, A. and Liu, H.W. Determination of the substrate binding mode to the active site iron of (S)-2-hydroxypropylphosphonic acid epoxidase using ¹⁷O-enriched substrates and substrate analogues. Biochemistry 46 (2007) 12628–12638. [DOI] [PMID: 17927218]
3.	Hidaka, T., Goda, M., Kuzuyama, T., Takei, N., Hidaka, M. and Seto, H. Cloning and nucleotide sequence of fosfomycin biosynthetic genes of Streptomyces wedmorensis. Mol. Gen. Genet. 249 (1995) 274–280. [PMID: 7500951]
4.	Liu, P., Mehn, M.P., Yan, F., Zhao, Z., Que, L., Jr. and Liu, H.W. Oxygenase activity in the self-hydroxylation of (S)-2-hydroxypropylphosphonic acid epoxidase involved in fosfomycin biosynthesis. J. Am. Chem. Soc. 126 (2004) 10306–10312. [DOI] [PMID: 15315444]
5.	Higgins, L.J., Yan, F., Liu, P., Liu, H.W. and Drennan, C.L. Structural insight into antibiotic fosfomycin biosynthesis by a mononuclear iron enzyme. Nature 437 (2005) 838–844. [DOI] [PMID: 16015285]
6.	Cameron, S., McLuskey, K., Chamberlayne, R., Hallyburton, I. and Hunter, W.N. Initiating a crystallographic analysis of recombinant (S)-2-hydroxypropylphosphonic acid epoxidase from Streptomyces wedmorensis. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 61 (2005) 534–536. [DOI] [PMID: 16511089]
7.	Wang, C., Chang, W.C., Guo, Y., Huang, H., Peck, S.C., Pandelia, M.E., Lin, G.M., Liu, H.W., Krebs, C. and Bollinger, J.M., Jr. Evidence that the fosfomycin-producing epoxidase, HppE, is a non-heme-iron peroxidase. Science 342 (2013) 991–995. [DOI] [PMID: 24114783]

[EC 1.11.1.23 created 2011 as EC 1.14.19.7, transferred 2014 to EC 1.11.1.23]

1.11.2.5

Accepted name:

3-methyl-L-tyrosine peroxygenase

Reaction:

3-methyl-L-tyrosine + H₂O₂ = 3-hydroxy-5-methyl-L-tyrosine + H₂O

For diagram of saframycin biosynthesis, click here

Other name(s):

SfmD; SacD; 3-methyltyrosine peroxidase; 3-methyl-L-tyrosine peroxidase

Systematic name:

3-methyl-L-tyrosine:hydrogen-peroxide oxidoreductase (3-hydroxy-5-methyl-L-tyrosine-forming)

Comments:

The heme-containing peroxygenase from the bacterium Streptomyces lavendulae is involved in biosynthesis of saframycin A, a potent antitumor antibiotic that belongs to the tetrahydroisoquinoline family.

Links to other databases:

References:

1.	Tang, M.C., Fu, C.Y. and Tang, G.L. Characterization of SfmD as a heme peroxidase that catalyzes the regioselective hydroxylation of 3-methyltyrosine to 3-hydroxy-5-methyltyrosine in saframycin A biosynthesis. J. Biol. Chem. 287 (2012) 5112–5121. [DOI] [PMID: 22187429]

[EC 1.11.2.5 created 2014]

1.13.11.78

Accepted name:

2-amino-1-hydroxyethylphosphonate dioxygenase (glycine-forming)

Reaction:

(2-amino-1-hydroxyethyl)phosphonate + O₂ = glycine + phosphate

Other name(s):

phnZ (gene name)

Systematic name:

2-amino-1-hydroxyethylphosphonate:oxygen 1-oxidoreductase (glycine-forming)

Comments:

Requires Fe²⁺. The enzyme, characterized from a marine bacterium, is involved in a 2-aminoethylphosphonate degradation pathway.

Links to other databases:

References:

1.	McSorley, F.R., Wyatt, P.B., Martinez, A., DeLong, E.F., Hove-Jensen, B. and Zechel, D.L. PhnY and PhnZ comprise a new oxidative pathway for enzymatic cleavage of a carbon-phosphorus bond. J. Am. Chem. Soc. 134 (2012) 8364–8367. [DOI] [PMID: 22564006]
2.	Worsdorfer, B., Lingaraju, M., Yennawar, N.H., Boal, A.K., Krebs, C., Bollinger, J.M., Jr. and Pandelia, M.E. Organophosphonate-degrading PhnZ reveals an emerging family of HD domain mixed-valent diiron oxygenases. Proc. Natl. Acad. Sci. USA 110 (2013) 18874–18879. [DOI] [PMID: 24198335]

[EC 1.13.11.78 created 2014]

1.13.11.79

Accepted name:

aerobic 5,6-dimethylbenzimidazole synthase

Reaction:

FMNH₂ + O₂ = 5,6-dimethylbenzimidazole + D-erythrose 4-phosphate + other product(s)

For diagram of FAD biosynthesis, click here

Other name(s):

BluB; flavin destructase

Systematic name:

FMNH₂ oxidoreductase (5,6-dimethylbenzimidazole-forming)

Comments:

The enzyme catalyses a complex oxygen-dependent conversion of reduced flavin mononucleotide to form 5,6-dimethylbenzimidazole, the lower ligand of vitamin B₁₂. This conversion involves many sequential steps in two distinct stages, and an alloxan intermediate that acts as a proton donor, a proton acceptor, and a hydride acceptor [4]. The C-2 of 5,6-dimethylbenzimidazole is derived from C-1′ of the ribityl group of FMNH₂ and 2-H from the ribityl 1′-pro-S hydrogen. While D-erythrose 4-phosphate has been shown to be one of the byproducts, the nature of the other product(s) has not been verified yet.

Links to other databases:

References:

1.	Gray, M.J. and Escalante-Semerena, J.C. Single-enzyme conversion of FMNH₂ to 5,6-dimethylbenzimidazole, the lower ligand of B₁₂. Proc. Natl. Acad. Sci. USA 104 (2007) 2921–2926. [DOI] [PMID: 17301238]
2.	Ealick, S.E. and Begley, T.P. Biochemistry: molecular cannibalism. Nature 446 (2007) 387–388. [DOI] [PMID: 17377573]
3.	Taga, M.E., Larsen, N.A., Howard-Jones, A.R., Walsh, C.T. and Walker, G.C. BluB cannibalizes flavin to form the lower ligand of vitamin B₁₂. Nature 446:449 (2007). [DOI] [PMID: 17377583]
4.	Wang, X.L. and Quan, J.M. Intermediate-assisted multifunctional catalysis in the conversion of flavin to 5,6-dimethylbenzimidazole by BluB: a density functional theory study. J. Am. Chem. Soc. 133 (2011) 4079–4091. [DOI] [PMID: 21344938]
5.	Collins, H.F., Biedendieck, R., Leech, H.K., Gray, M., Escalante-Semerena, J.C., McLean, K.J., Munro, A.W., Rigby, S.E., Warren, M.J. and Lawrence, A.D. Bacillus megaterium has both a functional BluB protein required for DMB synthesis and a related flavoprotein that forms a stable radical species. PLoS One 8:e55708 (2013). [DOI] [PMID: 23457476]

[EC 1.13.11.79 created 2010 as EC 1.14.99.40, transferred 2014 to EC 1.13.11.79, modified 2019]

1.14.11.45

Accepted name:

L-isoleucine 4-hydroxylase

Reaction:

L-isoleucine + 2-oxoglutarate + O₂ = (4S)-4-hydroxy-L-isoleucine + succinate + CO₂

Glossary:

(4S)-4-hydroxy-L-isoleucine = (2S,3R,4S)-2-amino-4-hydroxy-3-methylpentanoate

Other name(s):

ido (gene name)

Systematic name:

L-isoleucine,2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating)

Comments:

The enzyme, characterized from the bacterium Bacillus thuringiensis, can also catalyse the hydroxylation of L-leucine, L-norvaline, L-norleucine, and L-allo-isoleucine, as well as the sulfoxidation of L-methionine, L-ethionine, S-methyl-L-cysteine, S-ethyl-L-cysteine, and S-allyl-L-cysteine.

Links to other databases:

References:

1.	Kodera, T., Smirnov, S.V., Samsonova, N.N., Kozlov, Y.I., Koyama, R., Hibi, M., Ogawa, J., Yokozeki, K. and Shimizu, S. A novel L-isoleucine hydroxylating enzyme, L-isoleucine dioxygenase from Bacillus thuringiensis, produces (2S,3R,4S)-4-hydroxyisoleucine. Biochem. Biophys. Res. Commun. 390 (2009) 506–510. [DOI] [PMID: 19850012]
2.	Hibi, M., Kawashima, T., Kodera, T., Smirnov, S.V., Sokolov, P.M., Sugiyama, M., Shimizu, S., Yokozeki, K. and Ogawa, J. Characterization of Bacillus thuringiensis L-isoleucine dioxygenase for production of useful amino acids. Appl. Environ. Microbiol. 77 (2011) 6926–6930. [DOI] [PMID: 21821743]
3.	Hibi, M., Kawashima, T., Yajima, H., Smirnov, S.V., Kodera, T., Sugiyama, M., Shimizu, S., Yokozeki, K., and Ogawa, J. Enzymatic synthesis of chiral amino acid sulfoxides by Fe(II)/α ketoglutarate-dependent dioxygenase. Tetrahedron Asym. 24 (2013) 990–994.

[EC 1.14.11.45 created 2014]

1.14.11.46

Accepted name:

2-aminoethylphosphonate dioxygenase

Reaction:

(2-aminoethyl)phosphonate + 2-oxoglutarate + O₂ = (2-amino-1-hydroxyethyl)phosphonate + succinate + CO₂

Other name(s):

phnY (gene name)

Systematic name:

(2-aminoethyl)phosphonate,2-oxoglutarate:oxygen oxidoreductase (1-hydroxylating)

Comments:

Requires Fe²⁺ and ascorbate. The enzyme, characterized from an uncultured marine bacterium, is involved in a (2-aminoethyl)phosphonate degradation pathway.

Links to other databases:

References:

1.	McSorley, F.R., Wyatt, P.B., Martinez, A., DeLong, E.F., Hove-Jensen, B. and Zechel, D.L. PhnY and PhnZ comprise a new oxidative pathway for enzymatic cleavage of a carbon-phosphorus bond. J. Am. Chem. Soc. 134 (2012) 8364–8367. [DOI] [PMID: 22564006]

[EC 1.14.11.46 created 2014]

1.14.13.189

Accepted name:

5-methyl-1-naphthoate 3-hydroxylase

Reaction:

5-methyl-1-naphthoate + NADPH + H⁺ + O₂ = 3-hydroxy-5-methyl-1-naphthoate + NADP⁺ + H₂O

For diagram of the azinomycin biosynthesis (part of pathway), click here

Other name(s):

AziB1

Systematic name:

5-methyl-1-naphthoate,NADPH:oxygen oxidoreductase (3-hydroxylating)

Comments:

The enzyme from the bacterium Streptomyces sahachiroi is involved in the biosynthesis of 3-methoxy-5-methyl-1-naphthoate, a component of of the the antitumor antibiotic azinomycin B.

Links to other databases:

References:

1.	Ding, W., Deng, W., Tang, M., Zhang, Q., Tang, G., Bi, Y. and Liu, W. Biosynthesis of 3-methoxy-5-methyl naphthoic acid and its incorporation into the antitumor antibiotic azinomycin B. Mol. Biosyst. 6 (2010) 1071–1081. [DOI] [PMID: 20485749]

[EC 1.14.13.189 created 2014]

1.14.13.190

Transferred entry:

ferruginol synthase. Now EC 1.14.14.175, ferruginol synthase

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

1.14.13.191

Transferred entry:

ent-sandaracopimaradiene 3-hydroxylase. Now EC 1.14.14.70, ent-sandaracopimaradiene 3-hydroxylase

[EC 1.14.13.191 created 2014, deleted 2018]

1.14.13.192

Transferred entry:

oryzalexin E synthase. Now EC 1.14.14.122, oryzalexin E synthase

[EC 1.14.13.192 created 2014, deleted 2018]

1.14.13.193

Transferred entry:

oryzalexin D synthase. Now EC 1.14.14.123, oryzalexin D synthase

[EC 1.14.13.193 created 2014, deleted 2018]

1.14.13.194

Transferred entry:

phylloquinone ω-hydroxylase. Now EC 1.14.14.78, phylloquinone ω-hydroxylase

[EC 1.14.13.194 created 2014, deleted 2018]

1.14.14.15

Accepted name:

(3S)-3-amino-3-(3-chloro-4-hydroxyphenyl)propanoyl-[peptidyl-carrier protein SgcC2] monooxygenase

Reaction:

(3S)-3-amino-3-(3-chloro-4-hydroxyphenyl)propanoyl-[peptidyl-carrier protein SgcC2] + FADH₂ + O₂ = (3S)-3-amino-3-(3-chloro-4,5-dihydroxyphenyl)propanoyl-[peptidyl-carrier protein SgcC2] + FAD + H₂O

Other name(s):

SgcC

Systematic name:

(3S)-3-amino-3-(3-chloro-4-hydroxyphenyl)propanoyl-[peptidyl-carrier protein SgcC2],FADH₂:oxygen oxidoreductase (5-hydroxylating)

Comments:

The enzyme from the bacterium Streptomyces globisporus is involved in the biosynthesis of the (S)-3-chloro-5-hydroxy-β-tyrosine moiety prior to incorporation into the chromoprotein antitumor antibiotic C-1027.

Links to other databases:

References:

1.	Lin, S., Van Lanen, S.G. and Shen, B. Characterization of the two-component, FAD-dependent monooxygenase SgcC that requires carrier protein-tethered substrates for the biosynthesis of the enediyne antitumor antibiotic C-1027. J. Am. Chem. Soc. 130 (2008) 6616–6623. [DOI] [PMID: 18426211]

[EC 1.14.14.15 created 2014]

1.14.16.7

Accepted name:

phenylalanine 3-monooxygenase

Reaction:

L-phenylalanine + a 5,6,7,8-tetrahydropteridine + O₂ = 3-hydroxy-L-phenylalanine + a 4a-hydroxy-5,6,7,8-tetrahydropteridine

Glossary:

3-hydroxy-L-phenylalanine = meta-L-tyrosine = 3-(3-hydroxyphenyl)-L-alanine

Other name(s):

PacX; phenylalanine 3-hydroxylase

Systematic name:

L-phenylalanine,tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)

Comments:

The enzyme, characterized from the bacterium Streptomyces coeruleorubidus, forms 3-hydroxy-L-phenylalanine (i.e. m-L-tyrosine), which is one of the building blocks in the biosynthesis of the uridyl peptide antibiotics pacidamycins. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.

Links to other databases:

References:

1.	Zhang, W., Ames, B.D. and Walsh, C.T. Identification of phenylalanine 3-hydroxylase for meta-tyrosine biosynthesis. Biochemistry 50 (2011) 5401–5403. [DOI] [PMID: 21615132]

[EC 1.14.16.7 created 2014, modified 2019]

1.14.19.7

Transferred entry:

(S)-2-hydroxypropylphosphonic acid epoxidase. Now EC 1.11.1.23, (S)-2-hydroxypropylphosphonic acid epoxidase.

[EC 1.14.19.7 created 2011, deleted 2014]

1.14.99.40

Transferred entry:

5,6-dimethylbenzimidazole synthase. Now EC 1.13.11.79, 5,6-dimethylbenzimidazole synthase

[EC 1.14.99.40 created 2010, deleted 2014]

1.16.3.2

Accepted name:

bacterial non-heme ferritin

Reaction:

4 Fe(II) + O₂ + 6 H₂O = 4 [FeO(OH)] + 8 H⁺ (overall reaction)
(1a) 2 Fe(II) + O₂ + 4 H₂O = 2 [FeO(OH)] + 4 H⁺ + H₂O₂
(1b) 2 Fe(II) + H₂O₂ + 2 H₂O = 2 [FeO(OH)] + 4 H⁺

Glossary:

[FeO(OH)] = iron(III) oxide-hydroxide

Other name(s):

FtnA; HuHF

Systematic name:

Fe(II):oxygen oxidoreductase ([FeO(OH)]core-producing)

Comments:

Ferritins are intracellular iron-storage and detoxification proteins found in all kingdoms of life. They are formed from two subunits that co-assemble in various ratios to form a spherical protein shell. Thousands of mineralized iron atoms are stored within the core of the structure. The product of dioxygen reduction by the bacterial non-heme ferritin is hydrogen peroxide, which is consumed in a subsequent reaction.

Links to other databases:

References:

1.	Hudson, A.J., Andrews, S.C., Hawkins, C., Williams, J.M., Izuhara, M., Meldrum, F.C., Mann, S., Harrison, P.M. and Guest, J.R. Overproduction, purification and characterization of the Escherichia coli ferritin. Eur. J. Biochem. 218 (1993) 985–995. [DOI] [PMID: 8281950]
2.	Stillman, T.J., Hempstead, P.D., Artymiuk, P.J., Andrews, S.C., Hudson, A.J., Treffry, A., Guest, J.R. and Harrison, P.M. The high-resolution X-ray crystallographic structure of the ferritin (EcFtnA) of Escherichia coli; comparison with human H ferritin (HuHF) and the structures of the Fe³⁺ and Zn²⁺ derivatives. J. Mol. Biol. 307 (2001) 587–603. [DOI] [PMID: 11254384]
3.	Bou-Abdallah, F., Yang, H., Awomolo, A., Cooper, B., Woodhall, M.R., Andrews, S.C. and Chasteen, N.D. Functionality of the three-site ferroxidase center of Escherichia coli bacterial ferritin (EcFtnA). Biochemistry 53 (2014) 483–495. [DOI] [PMID: 24380371]

[EC 1.16.3.2 created 2014]

2.1.1.301

Accepted name:

cypemycin N-terminal methyltransferase

Reaction:

2 S-adenosyl-L-methionine + N-terminal L-alanine-[cypemycin] = 2 S-adenosyl-L-homocysteine + N-terminal N,N-dimethyl-L-alanine-[cypemycin]

Other name(s):

CypM

Systematic name:

S-adenosyl-L-methionine:N-terminal L-alanine-[cypemycin] N-methyltransferase

Comments:

The enzyme, isolated from the bacterium Streptomyces sp. OH-4156, can methylate a variety of linear oligopeptides, cyclic peptides such as nisin and haloduracin, and the ε-amino group of lysine [2]. Cypemycin is a peptide antibiotic, a member of the linaridins, a class of posttranslationally modified ribosomally synthesized peptides.

Links to other databases:

References:

1.	Claesen, J. and Bibb, M. Genome mining and genetic analysis of cypemycin biosynthesis reveal an unusual class of posttranslationally modified peptides. Proc. Natl. Acad. Sci. USA 107 (2010) 16297–16302. [DOI] [PMID: 20805503]
2.	Zhang, Q. and van der Donk, W.A. Catalytic promiscuity of a bacterial α-N-methyltransferase. FEBS Lett. 586 (2012) 3391–3397. [DOI] [PMID: 22841713]

[EC 2.1.1.301 created 2014]

2.1.1.302

Accepted name:

3-hydroxy-5-methyl-1-naphthoate 3-O-methyltransferase

Reaction:

S-adenosyl-L-methionine + 3-hydroxy-5-methyl-1-naphthoate = S-adenosyl-L-homocysteine + 3-methoxy-5-methyl-1-naphthoate

For diagram of the azinomycin biosynthesis (part of pathway), click here

Other name(s):

AziB2

Systematic name:

S-adenosyl-L-methionine:3-hydroxy-5-methyl-1-naphthoate 3-O-methyltransferase

Comments:

The enzyme from the bacterium Streptomyces sahachiroi is involved in the biosynthesis of 3-methoxy-5-methyl-1-naphthoate, a component of of the the antitumor antibiotic azinomycin B.

Links to other databases:

References:

1.	Ding, W., Deng, W., Tang, M., Zhang, Q., Tang, G., Bi, Y. and Liu, W. Biosynthesis of 3-methoxy-5-methyl naphthoic acid and its incorporation into the antitumor antibiotic azinomycin B. Mol. Biosyst. 6 (2010) 1071–1081. [DOI] [PMID: 20485749]

[EC 2.1.1.302 created 2014]

2.1.1.303

Accepted name:

2,7-dihydroxy-5-methyl-1-naphthoate 7-O-methyltransferase

Reaction:

S-adenosyl-L-methionine + 2,7-dihydroxy-5-methyl-1-naphthoate = S-adenosyl-L-homocysteine + 2-hydroxy-7-methoxy-5-methyl-1-naphthoate

For diagram of neocarzinostatin biosynthesis, click here

Other name(s):

NcsB1; neocarzinostatin O-methyltransferase

Systematic name:

S-adenosyl-L-methionine:2,7-dihydroxy-5-methyl-1-naphthoate 7-O-methyltransferase

Comments:

The enzyme from the bacterium Streptomyces carzinostaticus is involved in the biosynthesis of 2-hydroxy-7-methoxy-5-methyl-1-naphthoate. This compound is part of the enediyne chromophore of the antitumor antibiotic neocarzinostatin. In vivo the enzyme catalyses the regiospecific methylation at the 7-hydroxy group of its native substrate 2,7-dihydroxy-5-methyl-1-naphthoate. In vitro it also recognizes other dihydroxynaphthoic acids and catalyses their regiospecific O-methylation.

Links to other databases:

References:

1.	Luo, Y., Lin, S., Zhang, J., Cooke, H.A., Bruner, S.D. and Shen, B. Regiospecific O-methylation of naphthoic acids catalyzed by NcsB1, an O-methyltransferase involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin. J. Biol. Chem. 283 (2008) 14694–14702. [DOI] [PMID: 18387946]
2.	Cooke, H.A., Guenther, E.L., Luo, Y., Shen, B. and Bruner, S.D. Molecular basis of substrate promiscuity for the SAM-dependent O-methyltransferase NcsB1, involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin. Biochemistry 48 (2009) 9590–9598. [DOI] [PMID: 19702337]

[EC 2.1.1.303 created 2014]

2.1.1.304

Accepted name:

L-tyrosine C³-methyltransferase

Reaction:

S-adenosyl-L-methionine + L-tyrosine = S-adenosyl-L-homocysteine + 3-methyl-L-tyrosine

For diagram of saframycin biosynthesis, click here

Other name(s):

SfmM2; SacF

Systematic name:

S-adenosyl-L-methionine:L-tyrosine C³-methyltransferase

Comments:

The enzyme from the bacterium Streptomyces lavendulae is involved in biosynthesis of saframycin A, a potent antitumor antibiotic that belongs to the tetrahydroisoquinoline family.

Links to other databases:

References:

1.	Tang, M.C., Fu, C.Y. and Tang, G.L. Characterization of SfmD as a heme peroxidase that catalyzes the regioselective hydroxylation of 3-methyltyrosine to 3-hydroxy-5-methyltyrosine in saframycin A biosynthesis. J. Biol. Chem. 287 (2012) 5112–5121. [DOI] [PMID: 22187429]

[EC 2.1.1.304 created 2014]

2.1.1.305

Accepted name:

8-demethyl-8-α-L-rhamnosyltetracenomycin-C 2′-O-methyltransferase

Reaction:

S-adenosyl-L-methionine + 8-demethyl-8-α-L-rhamnosyltetracenomycin C = S-adenosyl-L-homocysteine + 8-demethyl-8-(2-O-methyl-α-L-rhamnosyl)tetracenomycin C

For diagram of elloramycin biosynthesis, click here

Glossary:

8-demethyl-8-α-L-rhamnosyltetracenomycin C = methyl (6aR,7S,10aR)-6a,7,10a,12-tetrahydroxy-8-methoxy-1-methyl-6,10,11-trioxo-3-α-L-rhamnosyloxy-6,6a,7,10,10a,11-hexahydrotetracene-2-carboxylate

Other name(s):

ElmMI

Systematic name:

S-adenosyl-L-methionine:8-demethyl-8-α-L-rhamnosyltetracenomycin-C 2′-O-methyltransferase

Comments:

The enzyme from the bacterium Streptomyces olivaceus is involved in the biosynthesis of the polyketide elloramycin.

Links to other databases:

References:

Patallo, E.P., Blanco, G., Fischer, C., Brana, A.F., Rohr, J., Mendez, C. and Salas, J.A. Deoxysugar methylation during biosynthesis of the antitumor polyketide elloramycin by Streptomyces olivaceus. Characterization of three methyltransferase genes. J. Biol. Chem. 276 (2001) 18765–18774. [DOI] [PMID: 11376004]

[EC 2.1.1.305 created 2014]

2.1.1.306

Accepted name:

8-demethyl-8-(2-methoxy-α-L-rhamnosyl)tetracenomycin-C 3′-O-methyltransferase

Reaction:

S-adenosyl-L-methionine + 8-demethyl-8-(2-O-methyl-α-L-rhamnosyl)tetracenomycin C = S-adenosyl-L-homocysteine + 8-demethyl-8-(2,3-di-O-methyl-α-L-rhamnosyl)tetracenomycin C

For diagram of elloramycin biosynthesis, click here

Glossary:

8-demethyl-8-α-L-rhamnosyltetracenomycin C = methyl (6aR,7S,10aR)-6a,7,10a,12-tetrahydroxy-8-methoxy-1-methyl-6,10,11-trioxo-3-α-L-rhamnosyloxy-6,6a,7,10,10a,11-hexahydrotetracene-2-carboxylate

Other name(s):

ElmMII

Systematic name:

S-adenosyl-L-methionine:8-demethyl-8-(2-methoxy-α-L-rhamnosyl)tetracenomycin-C 3′-O-methyltransferase

Comments:

The enzyme from the bacterium Streptomyces olivaceus is involved in the biosynthesis of the polyketide elloramycin.

Links to other databases:

References:

[EC 2.1.1.306 created 2014]

2.1.1.307

Accepted name:

8-demethyl-8-(2,3-dimethoxy-α-L-rhamnosyl)tetracenomycin-C 4′-O-methyltransferase

Reaction:

S-adenosyl-L-methionine + 8-demethyl-8-(2,3-di-O-methyl-α-L-rhamnosyl)tetracenomycin C = S-adenosyl-L-homocysteine + 8-demethyl-8-(2,3,4-tri-O-methyl-α-L-rhamnosyl)tetracenomycin C

For diagram of elloramycin biosynthesis, click here

Glossary:

8-demethyl-8-α-L-rhamnosyltetracenomycin C = methyl (6aR,7S,10aR)-6a,7,10a,12-tetrahydroxy-8-methoxy-1-methyl-6,10,11-trioxo-3-α-L-rhamnosyloxy-6,6a,7,10,10a,11-hexahydrotetracene-2-carboxylate

Other name(s):

ElmMIII

Systematic name:

S-adenosyl-L-methionine:8-demethyl-8-(2,3-di-O-methoxy-α-L-rhamnosyl)tetracenomycin-C 4′-O-methyltransferase

Comments:

The enzyme from the bacterium Streptomyces olivaceus is involved in the biosynthesis of the polyketide elloramycin.

Links to other databases:

References:

[EC 2.1.1.307 created 2014]

2.1.3.13

Deleted entry:

ATP carbamoyltransferase. The enzyme has been replaced by EC 6.1.2.2, nebramycin 5′ synthase.

[EC 2.1.3.13 created 2013, deleted 2014]

2.1.3.14

Deleted entry:

tobramycin carbamoyltransferase. The enzyme has been replaced by EC 6.1.2.2, nebramycin 5′ synthase

[EC 2.1.3.14 created 2013, deleted 2014]

2.3.1.233

Accepted name:

1,3,6,8-tetrahydroxynaphthalene synthase

Reaction:

5 malonyl-CoA = 1,3,6,8-tetrahydroxynaphthalene + 5 CoA + 5 CO₂ + H₂O

For diagram of polyketides biosynthesis, click here

Other name(s):

PKS1; THNS; SCO1206; RppA

Systematic name:

malonyl-CoA C-acyl transferase (1,3,6,8-tetrahydroxynaphthalene-forming)

Comments:

Isolated from the fungus Colletotrichum lagenarium [1], and the bacteria Streptomyces coelicolor [2,3] and Streptomyces peucetius [4]. It only uses malonyl-CoA, without invovement of acetyl-CoA.

Links to other databases:

References:

1.	Fujii, I., Mori, Y., Watanabe, A., Kubo, Y., Tsuji, G. and Ebizuka, Y. Enzymatic synthesis of 1,3,6,8-tetrahydroxynaphthalene solely from malonyl coenzyme A by a fungal iterative type I polyketide synthase PKS1. Biochemistry 39 (2000) 8853–8858. [DOI] [PMID: 10913297]
2.	Izumikawa, M., Shipley, P.R., Hopke, J.N., O'Hare, T., Xiang, L., Noel, J.P. and Moore, B.S. Expression and characterization of the type III polyketide synthase 1,3,6,8-tetrahydroxynaphthalene synthase from Streptomyces coelicolor A3(2). J Ind Microbiol Biotechnol 30 (2003) 510–515. [DOI] [PMID: 12905073]
3.	Austin, M.B., Izumikawa, M., Bowman, M.E., Udwary, D.W., Ferrer, J.L., Moore, B.S. and Noel, J.P. Crystal structure of a bacterial type III polyketide synthase and enzymatic control of reactive polyketide intermediates. J. Biol. Chem. 279 (2004) 45162–45174. [DOI] [PMID: 15265863]
4.	Ghimire, G.P., Oh, T.J., Liou, K. and Sohng, J.K. Identification of a cryptic type III polyketide synthase (1,3,6,8-tetrahydroxynaphthalene synthase) from Streptomyces peucetius ATCC 27952. Mol. Cells 26 (2008) 362–367. [PMID: 18612244]

[EC 2.3.1.233 created 2014]

*EC

2.4.1.208

Accepted name:

diglucosyl diacylglycerol synthase (1,2-linking)

Reaction:

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

Other name(s):

monoglucosyl diacylglycerol (1→2) glucosyltransferase; MGlcDAG (1→2) glucosyltransferase; DGlcDAG synthase (ambiguous); UDP-glucose:1,2-diacyl-3-O-(α-D-glucopyranosyl)-sn-glycerol (1→2) glucosyltransferase; diglucosyl diacylglycerol synthase

Systematic name:

UDP-α-D-glucose:1,2-diacyl-3-O-(α-D-glucopyranosyl)-sn-glycerol 2-glucosyltransferase

Comments:

The enzyme from Acholeplasma laidlawii requires Mg²⁺.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 168680-19-1

References:

1.	Karlsson, O.P., Rytomaa, M., Dahlqvist, A., Kinnunen, P.K., Wieslander, A. Correlation between bilayer lipid dynamics and activity of the diglucosyldiacylglycerol synthase from Acholeplasma laidlawii membranes. Biochemistry 35 (1996) 10094–10102. [DOI] [PMID: 8756472]

[EC 2.4.1.208 created 1999, modified 2014]

2.4.1.325

Accepted name:

TDP-N-acetylfucosamine:lipid II N-acetylfucosaminyltransferase

Reaction:

dTDP-4-acetamido-4,6-dideoxy-α-D-galactose + N-acetyl-β-D-mannosaminouronyl-(1→4)-N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol = dTDP + 4-acetamido-4,6-dideoxy-α-D-galactosyl-(1→4)-N-acetyl-β-D-mannosaminouronyl-(1→4)-N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol

Glossary:

dTDP-4-acetamido-4,6-dideoxy-α-D-galactose = dTDP-N-acetyl-α-D-fucosamine
a lipid II = an undecaprenyldiphospho-N-acetyl-(N-acetylglucosaminyl)muramoyl peptide; the peptide element refers to L-alanyl-D-γ-glutamyl-L-lysyl/meso-2,6-diaminopimelyl-D-alanyl-D-alanine or a modified version thereof = an undecaprenyldiphospho-4-O-(N-acetyl-β-D-glucosaminyl)-3-O-peptidyl-α-N-acetylmuramate; the peptide element refers to L-alanyl-D-γ-glutamyl-L-lysyl/meso-2,6-diaminopimelyl-D-alanyl-D-alanine or a modified version thereof
lipid III = N-acetyl-β-D-fucosyl-(1→4)-N-acetyl-β-D-mannosaminouronyl-(1→4)-N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol

Other name(s):

TDP-Fuc4NAc:lipid II Fuc4NAc-transferase; TDP-Fuc4NAc:lipid II Fuc4NAc transferase; wecF (gene name)

Systematic name:

dTDP-N-acetyl-α-D-fucose:N-acetyl-β-D-mannosaminouronyl-(1→4)-N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol N-acetylfucosaminyltransferase

Comments:

Involved in the enterobacterial common antigen (ECA) biosynthesis in the bacterium Escherichia coli. The trisaccharide of the product (lipid III) is the repeat unit of ECA.

Links to other databases:

References:

1.	Rahman, A., Barr, K. and Rick, P.D. Identification of the structural gene for the TDP-Fuc4NAc:lipid II Fuc4NAc transferase involved in synthesis of enterobacterial common antigen in Escherichia coli K-12. J. Bacteriol. 183 (2001) 6509–6516. [DOI] [PMID: 11673418]

[EC 2.4.1.325 created 2014]

2.4.1.326

Accepted name:

aklavinone 7-L-rhodosaminyltransferase

Reaction:

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

For diagram of aklavinone biosynthesis, click here

Glossary:

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

Other name(s):

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

Systematic name:

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

Comments:

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

Links to other databases:

References:

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

[EC 2.4.1.326 created 2014, modified 2015]

2.4.1.327

Accepted name:

aclacinomycin-T 2-deoxy-L-fucose transferase

Reaction:

dTDP-2-deoxy-β-L-fucose + aclacinomycin T = dTDP + aclacinomycin S

For diagram of aclacinomycin A and Y biosynthesis, click here

Glossary:

idarubicin = (7S,9S)-9-acetyl-7-(3-amino-2,3,6-trideoxy-β-L-lyxo-hexosyloxy)-6,9,11-trihydroxy-7,8,9,10-tetrahydrotetracene-5,12-dione
aclacinomycin S = 7-O-(2-deoxy-α-L-fucosyl-(1→4)-rhodosaminyl)aklavinone
aclacinomycin T = 7-O-(α-L-rhodosaminyl)aklavinone

Other name(s):

AknK

Systematic name:

dTDP-2-deoxy-β-L-fucose:7-(α-L-rhodosaminyl)aklavinone 2-deoxy-α-L-fucosyltransferase

Comments:

The enzyme, isolated from the bacterium Streptomyces galilaeus, is involved in the biosynthesis of other aclacinomycins. Also acts on idarubicin. It will slowly add a second 2-deoxy-L-fucose unit to aclacinomycin S in vitro.

Links to other databases:

References:

1.	Lu, W., Leimkuhler, C., Oberthur, M., Kahne, D. and Walsh, C.T. AknK is an L-2-deoxyfucosyltransferase in the biosynthesis of the anthracycline aclacinomycin A. Biochemistry 43 (2004) 4548–4558. [DOI] [PMID: 15078101]

[EC 2.4.1.327 created 2014]

2.4.1.328

Accepted name:

erythronolide mycarosyltransferase

Reaction:

dTDP-β-L-mycarose + erythronolide B = dTDP + 3-α-L-mycarosylerythronolide B

For diagram of erythromycin biosynthesis, click here

Glossary:

dTDP-β-L-mycarose = dTDP-2,6-dideoxy-3-C-methyl-β-L-ribo-hexose
L-mycarose = 2,6-dideoxy-3-C-methyl-L-ribo-hexose

Other name(s):

EryBV

Systematic name:

dTDP-β-L-mycarose:erythronolide B L-mycarosyltransferase

Comments:

Isolated from the bacterium Saccharopolyspora erythraea. The enzyme is involved in the biosynthesis of the antibiotic erythromycin.

Links to other databases:

References:

1.	Zhang, C., Fu, Q., Albermann, C., Li, L. and Thorson, J.S. The in vitro characterization of the erythronolide mycarosyltransferase EryBV and its utility in macrolide diversification. ChemBioChem 8 (2007) 385–390. [DOI] [PMID: 17262863]

[EC 2.4.1.328 created 2014]

2.5.1.121

Accepted name:

5,10-dihydrophenazine-1-carboxylate 9-dimethylallyltransferase

Reaction:

prenyl diphosphate + 5,10-dihydrophenazine-1-carboxylate = diphosphate + 9-prenyl-5,10-dihydrophenazine-1-carboxylate

Glossary:

9-prenyl-5,10-dihydrophenazine-1-carboxylate = 9-(3-methylbut-2-en-1-yl)-5,10-dihydrophenazine-1-carboxylate

Other name(s):

PpzP; dihydrophenazine-1-carboxylate dimethylallyltransferase; 5,10-dihydrophenazine 1-carboxylate dimethylallyltransferase; dimethylallyl diphosphate:5,10-dihydrophenazine-1-carboxylate 9-dimethylallyltransferase

Systematic name:

prenyl-diphosphate:5,10-dihydrophenazine-1-carboxylate 9-prenyltransferase

Comments:

The enzyme is involved in the biosynthesis of prenylated phenazines by the bacterium Streptomyces anulatus. It is specific for both prenyl diphosphate and 5,10-dihydrophenazine-1-carboxylate.

Links to other databases:

References:

1.	Saleh, O., Gust, B., Boll, B., Fiedler, H.P. and Heide, L. Aromatic prenylation in phenazine biosynthesis: dihydrophenazine-1-carboxylate dimethylallyltransferase from Streptomyces anulatus. J. Biol. Chem. 284 (2009) 14439–14447. [DOI] [PMID: 19339241]

[EC 2.5.1.121 created 2014]

2.5.1.122

Accepted name:

4-O-dimethylallyl-L-tyrosine synthase

Reaction:

prenyl diphosphate + L-tyrosine = diphosphate + 4-O-prenyl-L-tyrosine

Other name(s):

SirD; dimethylallyl diphosphate:L-tyrosine 4-O-dimethylallyltransferase

Systematic name:

prenyl-diphosphate:L-tyrosine 4-O-prenyltransferase

Comments:

The enzyme is involved in biosynthesis of the phytotoxin sirodesmin PL by the phytopathogenic ascomycete Leptosphaeria maculans.

Links to other databases:

References:

1.	Kremer, A. and Li, S.M. A tyrosine O-prenyltransferase catalyses the first pathway-specific step in the biosynthesis of sirodesmin PL. Microbiology 156 (2010) 278–286. [DOI] [PMID: 19762440]
2.	Zou, H.X., Xie, X., Zheng, X.D. and Li, S.M. The tyrosine O-prenyltransferase SirD catalyzes O-, N-, and C-prenylations. Appl. Microbiol. Biotechnol. 89 (2011) 1443–1451. [DOI] [PMID: 21038099]

[EC 2.5.1.122 created 2014]

2.5.1.123

Accepted name:

flaviolin linalyltransferase

Reaction:

geranyl diphosphate + flaviolin = 3-linalylflaviolin + diphosphate

For diagram of flaviolin metabolism, click here

Glossary:

flaviolin = 2,5,7-trihydroxynaphthalene-1,4-dione
3-linalylflaviolin = 2,5,7-trihydroxy-3-(3,7-dimethylocta-1,6-dien-3-yl)naphthalene-1,4-dione

Other name(s):

Fnq26

Systematic name:

geranyl-diphosphate:flaviolin 3-linalyltransferase

Comments:

Does not require Mg²⁺ or any other metal ions. Isolated from the bacterium Streptomyces cinnamonensis. In vitro the enzyme also forms traces of 3-geranylflaviolin.

Links to other databases:

References:

1.	Haagen, Y., Unsold, I., Westrich, L., Gust, B., Richard, S.B., Noel, J.P. and Heide, L. A soluble, magnesium-independent prenyltransferase catalyzes reverse and regular C-prenylations and O-prenylations of aromatic substrates. FEBS Lett. 581 (2007) 2889–2893. [DOI] [PMID: 17543953]

[EC 2.5.1.123 created 2014]

2.7.1.183

Accepted name:

glycoprotein-mannosyl O⁶-kinase

Reaction:

ATP + O³-[N-acetyl-β-D-galactosaminyl-(1→3)-N-acetyl-β-D-glucosaminyl-(1→4)-α-D-mannosyl]-L-threonyl/L-seryl-[protein] = ADP + O³-[N-acetyl-β-D-galactosaminyl-(1→3)-N-acetyl-β-D-glucosaminyl-(1→4)-α-D-(6-phospho)mannosyl]-L-threonyl/L-seryl-[protein]

For diagram of glycoprotein biosynthesis, click here

Other name(s):

SGK196; protein O-mannose kinase

Systematic name:

ATP:O³-[N-acetyl-β-D-galactosaminyl-(1→3)-N-acetyl-β-D-glucosaminyl-(1→4)-α-D-mannosyl]-L-threonyl/L-seryl-[protein] 6-phosphotransferase

Comments:

In humans this phosphorylated trisaccharide is attached to an L-threonine residue of α-dystroglycan, an extracellular peripheral glycoprotein that acts as a receptor for extracellular matrix proteins containing laminin-G domains, and is important for its activity.

Links to other databases:

References:

1.	Yoshida-Moriguchi, T., Willer, T., Anderson, M.E., Venzke, D., Whyte, T., Muntoni, F., Lee, H., Nelson, S.F., Yu, L. and Campbell, K.P. SGK196 is a glycosylation-specific O-mannose kinase required for dystroglycan function. Science 341 (2013) 896–899. [DOI] [PMID: 23929950]

[EC 2.7.1.183 created 2014]

2.7.1.184

Accepted name:

sulfofructose kinase

Reaction:

ATP + 6-deoxy-6-sulfo-D-fructose = ADP + 6-deoxy-6-sulfo-D-fructose 1-phosphate

For diagram of sulphoglycolysis of sulfoquinovose, click here

Other name(s):

yihV (gene name)

Systematic name:

ATP:6-deoxy-6-sulfo-D-fructose 1-phosphotransferase

Comments:

Links to other databases:

References:

1.	Denger, K., Weiss, M., Felux, A.K., Schneider, A., Mayer, C., Spiteller, D., Huhn, T., Cook, A.M. and Schleheck, D. Sulphoglycolysis in Escherichia coli K-12 closes a gap in the biogeochemical sulphur cycle. Nature 507 (2014) 114–117. [DOI] [PMID: 24463506]

[EC 2.7.1.184 created 2014]

*EC

2.7.7.86

Accepted name:

cyclic GMP-AMP synthase

Reaction:

ATP + GTP = 2 diphosphate + cyclic Gp(2′-5′)Ap(3′-5′) (overall reaction)
(1a) ATP + GTP = pppGp(2′-5′)A + diphosphate
(1b) pppGp(2′-5′)A = cyclic Gp(2′-5′)Ap(3′-5′) + diphosphate

Glossary:

cyclic Gp(2′-5′)Ap(3′-5′) = cyclo[(3′→5′)-guanylyl-(2′→5′)-adenylyl]

Other name(s):

cGAMP synthase; cGAS

Systematic name:

ATP:GTP adenylyltransferase (cyclizing)

Comments:

Cyclic Gp(2′-5′)Ap(3′-5′) is a signalling molecule in mammalian cells that triggers the production of type I interferons and other cytokines.

Links to other databases:

References:

1.	Sun, L., Wu, J., Du, F., Chen, X. and Chen, Z.J. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339 (2013) 786–791. [DOI] [PMID: 23258413]
2.	Ablasser, A., Goldeck, M., Cavlar, T., Deimling, T., Witte, G., Rohl, I., Hopfner, K.P., Ludwig, J. and Hornung, V. cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING. Nature 498 (2013) 380–384. [DOI] [PMID: 23722158]

[EC 2.7.7.86 created 2013, modified 2014]

2.8.2.37

Accepted name:

trehalose 2-sulfotransferase

Reaction:

3′-phosphoadenylyl sulfate + α,α-trehalose = adenosine 3′,5′-bisphosphate + 2-O-sulfo-α,α-trehalose

Glossary:

2-O-sulfo-α,α-trehalose = trehalose 2-sulfate = α-D-glucopyranosyl 2-O-sulfo-α-D-glucopyranoside

Other name(s):

Stf0 sulfotransferase; 3′-phosphoadenylyl-sulfate:α,α-trehalose 2-sulfotransferase

Systematic name:

3′-phosphoadenylyl-sulfate:α,α-trehalose 2-sulfonotransferase

Comments:

The sulfation of trehalose in the bacterium Mycobacterium tuberculosis is required for the biosynthesis of sulfolipid-1.

Links to other databases:

References:

1.	Mougous, J.D., Petzold, C.J., Senaratne, R.H., Lee, D.H., Akey, D.L., Lin, F.L., Munchel, S.E., Pratt, M.R., Riley, L.W., Leary, J.A., Berger, J.M. and Bertozzi, C.R. Identification, function and structure of the mycobacterial sulfotransferase that initiates sulfolipid-1 biosynthesis. Nat. Struct. Mol. Biol. 11 (2004) 721–729. [DOI] [PMID: 15258569]
2.	Pi, N., Hoang, M.B., Gao, H., Mougous, J.D., Bertozzi, C.R. and Leary, J.A. Kinetic measurements and mechanism determination of Stf0 sulfotransferase using mass spectrometry. Anal. Biochem. 341 (2005) 94–104. [DOI] [PMID: 15866533]

[EC 2.8.2.37 created 2014]

3.1.1.96

Accepted name:

D-aminoacyl-tRNA deacylase

Reaction:

(1) a D-aminoacyl-tRNA + H₂O = a D-amino acid + tRNA
(2) glycyl-tRNA^Ala + H₂O = glycine + tRNA^Ala

Other name(s):

Dtd2; D-Tyr-tRNA(Tyr) deacylase; D-Tyr-tRNA^Tyr deacylase; D-tyrosyl-tRNA^Tyr aminoacylhydrolase; dtdA (gene name)

Systematic name:

D-aminoacyl-tRNA aminoacylhydrolase

Comments:

The enzyme, found in all domains of life, can cleave mischarged glycyl-tRNA^Ala [5]. The enzyme from Escherichia coli can cleave D-tyrosyl-tRNA^Tyr, D-aspartyl-tRNA^Asp and D-tryptophanyl-tRNA^Trp [1]. Whereas the enzyme from the archaeon Pyrococcus abyssi is a zinc protein, the enzyme from Escherichia coli does not carry any zinc [2].

Links to other databases:

References:

1.	Soutourina, J., Plateau, P. and Blanquet, S. Metabolism of D-aminoacyl-tRNAs in Escherichia coli and Saccharomyces cerevisiae cells. J. Biol. Chem. 275 (2000) 32535–32542. [DOI] [PMID: 10918062]
2.	Ferri-Fioni, M.L., Schmitt, E., Soutourina, J., Plateau, P., Mechulam, Y. and Blanquet, S. Structure of crystalline D-Tyr-tRNA(Tyr) deacylase. A representative of a new class of tRNA-dependent hydrolases. J. Biol. Chem. 276 (2001) 47285–47290. [DOI] [PMID: 11568181]
3.	Ferri-Fioni, M.L., Fromant, M., Bouin, A.P., Aubard, C., Lazennec, C., Plateau, P. and Blanquet, S. Identification in archaea of a novel D-Tyr-tRNA^Tyr deacylase. J. Biol. Chem. 281 (2006) 27575–27585. [DOI] [PMID: 16844682]
4.	Wydau, S., Ferri-Fioni, M.L., Blanquet, S. and Plateau, P. GEK1, a gene product of Arabidopsis thaliana involved in ethanol tolerance, is a D-aminoacyl-tRNA deacylase. Nucleic Acids Res. 35 (2007) 930–938. [DOI] [PMID: 17251192]
5.	Pawar, K.I., Suma, K., Seenivasan, A., Kuncha, S.K., Routh, S.B., Kruparani, S.P. and Sankaranarayanan, R. Role of D-aminoacyl-tRNA deacylase beyond chiral proofreading as a cellular defense against glycine mischarging by AlaRS. Elife 6:e24001 (2017). [DOI] [PMID: 28362257]

[EC 3.1.1.96 created 2014, modified 2019]

3.1.4.57

Accepted name:

phosphoribosyl 1,2-cyclic phosphate 1,2-diphosphodiesterase

Reaction:

(1) 5-phospho-α-D-ribose 1,2-cyclic phosphate + H₂O = D-ribofuranose 2,5-bisphosphate
(2) D-ribofuranose 2,5-bisphosphate + H₂O = D-ribofuranose 5-phosphate + phosphate

Other name(s):

cyclic phosphate dihydrolase; phnPP (gene name)

Systematic name:

5-phospho-α-D-ribose 1,2-cyclic phosphate 1,2-diphosphophosphohydrolase

Comments:

The enzyme, characterized from the bacterium Eggerthella lenta, is involed in degradation of methylphosphonate.

Links to other databases:

References:

1.	Ghodge, S.V., Cummings, J.A., Williams, H.J. and Raushel, F.M. Discovery of a cyclic phosphodiesterase that catalyzes the sequential hydrolysis of both ester bonds to phosphorus. J. Am. Chem. Soc. 135 (2013) 16360–16363. [DOI] [PMID: 24147537]

[EC 3.1.4.57 created 2014]

3.1 Acting on ester bonds

3.1.12 Exodeoxyribonucleases producing 3′-phosphomonoesters

3.1.12.1

Accepted name:

5′ to 3′ exodeoxyribonuclease (nucleoside 3′-phosphate-forming)

Reaction:

exonucleolytic cleavage in the 5′- to 3′-direction to yield nucleoside 3′-phosphates

Other name(s):

Cas4; 5′ to 3′ single stranded DNA exonuclease

Comments:

Preference for single-stranded DNA. The enzyme from the archaeon Sulfolobus solfataricus contains a [4Fe-4S] cluster and requires a divalent metal cation, such as Mg²⁺ or Mn²⁺, for activity.

Links to other databases:

References:

1.	Zhang, J., Kasciukovic, T. and White, M.F. The CRISPR associated protein Cas4 Is a 5′ to 3′ DNA exonuclease with an iron-sulfur cluster. PLoS One 7:e47232 (2012). [DOI] [PMID: 23056615]
2.	Lemak, S., Beloglazova, N., Nocek, B., Skarina, T., Flick, R., Brown, G., Popovic, A., Joachimiak, A., Savchenko, A. and Yakunin, A.F. Toroidal structure and DNA cleavage by the CRISPR-associated [4Fe-4S] cluster containing Cas4 nuclease SSO0001 from Sulfolobus solfataricus. J. Am. Chem. Soc. 135 (2013) 17476–17487. [DOI] [PMID: 24171432]

[EC 3.1.12.1 created 2014]

*EC

3.5.1.46

Accepted name:

6-aminohexanoate-oligomer exohydrolase

Reaction:

(1) [N-(6-aminohexanoyl)]_n + H₂O = [N-(6-aminohexanoyl)]_n-1 + 6-aminohexanoate
(2) N-(6-aminohexanoyl)-6-aminohexanoate + H₂O = 2 6-aminohexanoate

Other name(s):

6-aminohexanoate-dimer hydrolase; nylB (gene name); 6-aminohexanoic acid oligomer hydrolase (ambiguous); N-(6-aminohexanoyl)-6-aminohexanoate amidohydrolase; nylon-6 hydrolase (ambiguous)

Systematic name:

N-(6-aminohexanoyl)-6-aminohexanoate exoamidohydrolase

Comments:

The enzyme is involved in degradation of nylon-6 oligomers. It degrades linear oligomers of 6-aminohexanoate with a degree of polymerization of 2–20 by exo-type cleavage, removing residues sequentially from the N-terminus. Activity decreases with the increase of the polymerization number of the oligomer. cf. EC 3.5.1.117, 6-aminohexanoate-oligomer endohydrolase and EC 3.5.2.12, 6-aminohexanoate-cyclic-dimer hydrolase.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 75216-15-8

References:

1.	Kinoshita, S., Terada, T., Taniguchi, T., Takeney, Y., Masuda, S., Matsunaga, N. and Okada, H. Purification and characterization of 6-aminohexanoic-acid-oligomer hydrolase of Flavobacterium sp. KI72. Eur. J. Biochem. 116 (1981) 547–551. [DOI] [PMID: 7262074]

[EC 3.5.1.46 created 1983, modified 2014]

3.5.1.117

Accepted name:

6-aminohexanoate-oligomer endohydrolase

Reaction:

[N-(6-aminohexanoyl)]_n + H₂O = [N-(6-aminohexanoyl)]_n-x + [N-(6-aminohexanoyl)]_x

Other name(s):

endo-type 6-aminohexanoate oligomer hydrolase; Ahx endo-type-oligomer hydrolase; 6-aminohexanoate oligomer hydrolase; Ahx-oligomer hydrolase; nylon hydrolase; nylon-oligomer hydrolase; NylC; nylon-6 hydrolase (ambiguous)

Systematic name:

6-aminohexanoate oligomer endoamidohydrolase

Comments:

The enzyme is involved in degradation of nylon-6 oligomers. It degrades linear or cyclic oligomers of poly(6-aminohexanoate) with a degree of polymerization greater than three (n > 3) by endo-type cleavage, to oligomers of a length of two or more (2 ≤ x < n). It shows negligible activity with N-(6-aminohexanoyl)-6-aminohexanoate (cf. EC 3.5.1.46, 6-aminohexanoate-oligomer exo hydrolase) or with 1,8-diazacyclotetradecane-2,9-dione (cf. EC 3.5.2.12, 6-aminohexanoate-cyclic-dimer hydrolase).

Links to other databases:

References:

1.	Kakudo, S., Negoro, S., Urabe, I. and Okada, H. Nylon oligomer degradation gene, nylC, on plasmid pOAD2 from a Flavobacterium strain encodes endo-type 6-aminohexanoate oligomer hydrolase: purification and characterization of the nylC gene product. Appl. Environ. Microbiol. 59 (1993) 3978–3980. [PMID: 8285701]
2.	Yasuhira, K., Tanaka, Y., Shibata, H., Kawashima, Y., Ohara, A., Kato, D., Takeo, M. and Negoro, S. 6-Aminohexanoate oligomer hydrolases from the alkalophilic bacteria Agromyces sp. strain KY5R and Kocuria sp. strain KY2. Appl. Environ. Microbiol. 73 (2007) 7099–7102. [DOI] [PMID: 17827307]
3.	Negoro, S., Shibata, N., Tanaka, Y., Yasuhira, K., Shibata, H., Hashimoto, H., Lee, Y.H., Oshima, S., Santa, R., Oshima, S., Mochiji, K., Goto, Y., Ikegami, T., Nagai, K., Kato, D., Takeo, M. and Higuchi, Y. Three-dimensional structure of nylon hydrolase and mechanism of nylon-6 hydrolysis. J. Biol. Chem. 287 (2012) 5079–5090. [DOI] [PMID: 22187439]

[EC 3.5.1.117 created 2014]

*EC

3.5.4.17

Accepted name:

adenosine-phosphate deaminase

Reaction:

(1) AMP + H₂O = IMP + NH₃
(2) ADP + H₂O = IDP + NH₃
(3) ATP + H₂O = ITP + NH₃

Glossary:

IMP = inosine 5′-phosphate
AMP = adenosine 5′-phosphate

Other name(s):

adenylate deaminase; adenine nucleotide deaminase; adenosine (phosphate) deaminase

Systematic name:

adenosine-phosphate aminohydrolase

Comments:

Acts on AMP, ADP, ATP, NAD⁺ and adenosine, in decreasing order of activity. The bacterial enzyme can also accept the deoxy derivatives. cf. EC 3.5.4.6, AMP deaminase.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 37289-20-6

References:

1.	Su, J.-C., Li, C.-C. and Ting, C.C. A new adenylate deaminase from red marine alga Porphyra crispata. Biochemistry 5 (1966) 536–543. [PMID: 5940938]
2.	Yates, M.G. A non-specific adenine nucleotide deaminase from Desulfovibrio desulfuricans. Biochim. Biophys. Acta 171 (1969) 299–310. [DOI] [PMID: 5773435]

[EC 3.5.4.17 created 1972, modified 1980, modified 2014]

*EC

3.5.99.7

Accepted name:

1-aminocyclopropane-1-carboxylate deaminase

Reaction:

1-aminocyclopropane-1-carboxylate + H₂O = 2-oxobutanoate + NH₃ (overall reaction)
(1a) 1-aminocyclopropane-1-carboxylate = 2-aminobut-2-enoate
(1b) 2-aminobut-2-enoate = 2-iminobutanoate (spontaneous)
(1c) 2-iminobutanoate + H₂O = 2-oxobutanoate + NH₃ (spontaneous)

Other name(s):

1-aminocyclopropane-1-carboxylate endolyase (deaminating); ACC deaminase; 1-aminocyclopropane carboxylic acid deaminase

Systematic name:

1-aminocyclopropane-1-carboxylate aminohydrolase (isomerizing)

Comments:

A pyridoxal 5′-phosphate enzyme. The enzyme, found in certain soil bacteria and fungi, catalyses the ring opening of 1-aminocyclopropane-1-carboxylate, the immediate precursor to ethylene, an important plant hormone that regulates fruit ripening and other processes. The enzyme releases an unstable enamine product that tautomerizes to an imine form, which undergoes a hydrolytic deamination. The latter reaction, which can occur spontaneously, can also be catalysed by EC 3.5.99.10, 2-iminobutanoate/2-iminopropanoate deaminase. The enzyme has been used to make fruit ripening dependent on externally added ethylene, as it removes the substrate for endogenous ethylene formation.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 69553-48-6

References:

1.	Honma, M. and Shimomura, T. Metabolism of 1-aminocyclopropane-1-carboxylic acid. Agric. Biol. Chem. 42 (1978) 1825–1831.
2.	Yao, M., Ose, T., Sugimoto, H., Horiuchi, A., Nakagawa, A., Wakatsuki, S., Yokoi, D., Murakami, T., Honma, M. and Tanaka, I. Crystal structure of 1-aminocyclopropane-1-carboxylate deaminase from Hansenula saturnus. J. Biol. Chem. 275 (2000) 34557–34565. [DOI] [PMID: 10938279]
3.	Thibodeaux, C.J. and Liu, H.W. Mechanistic studies of 1-aminocyclopropane-1-carboxylate deaminase: characterization of an unusual pyridoxal 5′-phosphate-dependent reaction. Biochemistry 50 (2011) 1950–1962. [DOI] [PMID: 21244019]

[EC 3.5.99.7 created 1981 as EC 4.1.99.4, transferred 2002 to EC 3.5.99.7, modified 2014]

3.13.1.4

Accepted name:

3-sulfinopropanoyl-CoA desulfinase

Reaction:

3-sulfinopropanoyl-CoA + H₂O = propanoyl-CoA + sulfite

Other name(s):

3SP-CoA desulfinase; AcdDPN7; 3-sulfinopropionyl-CoA desulfinase

Systematic name:

3-sulfinopropanoyl-CoA sulfinohydrolase

Comments:

The enzyme from the β-proteobacterium Advenella mimigardefordensis contains one non-covalently bound FAD per subunit.

Links to other databases:

References:

1.	Schurmann, M., Deters, A., Wubbeler, J.H. and Steinbuchel, A. A novel 3-sulfinopropionyl coenzyme A (3SP-CoA) desulfinase from Advenella mimigardefordensis strain DPN7T acting as a key enzyme during catabolism of 3,3′-dithiodipropionic acid is a member of the acyl-CoA dehydrogenase superfamily. J. Bacteriol. 195 (2013) 1538–1551. [DOI] [PMID: 23354747]
2.	Schurmann, M., Demming, R.M., Krewing, M., Rose, J., Wubbeler, J.H. and Steinbuchel, A. Identification of 3-sulfinopropionyl coenzyme A (CoA) desulfinases within the Acyl-CoA dehydrogenase superfamily. J. Bacteriol. 196 (2014) 882–893. [DOI] [PMID: 24317404]

[EC 3.13.1.4 created 2014]

4.1.1.98

Accepted name:

4-hydroxy-3-polyprenylbenzoate decarboxylase

Reaction:

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

For diagram of ubiquinol biosynthesis, click here

Other name(s):

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

Systematic name:

4-hydroxy-3-polyprenylbenzoate carboxy-lyase

Comments:

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

Links to other databases:

References:

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

[EC 4.1.1.98 created 2014, modified 2015]

4.1.2.57

Accepted name:

sulfofructosephosphate aldolase

Reaction:

6-deoxy-6-sulfo-D-fructose 1-phosphate = glycerone phosphate + (2S)-3-sulfolactaldehyde

For diagram of sulphoglycolysis of sulfoquinovose, click here

Glossary:

glycerone phosphate = dihydroxyacetone phosphate = 3-hydroxy-2-oxopropyl phosphate
(2S)-3-sulfolactaldehyde = (2S)-2-hydroxy-3-oxopropane-1-sulfonate

Other name(s):

yihT (gene name)

Systematic name:

6-deoxy-6-sulfofructose-1-phosphate (2S)-3-sulfolactaldehyde-lyase (glycerone-phosphate-forming)

Comments:

Links to other databases:

References:

1.	Denger, K., Weiss, M., Felux, A.K., Schneider, A., Mayer, C., Spiteller, D., Huhn, T., Cook, A.M. and Schleheck, D. Sulphoglycolysis in Escherichia coli K-12 closes a gap in the biogeochemical sulphur cycle. Nature 507 (2014) 114–117. [DOI] [PMID: 24463506]

[EC 4.1.2.57 created 2014]

*EC

4.2.1.134

Accepted name:

very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase

Reaction:

a very-long-chain (3R)-3-hydroxyacyl-CoA = a very-long-chain trans-2,3-dehydroacyl-CoA + H₂O

Glossary:

a very-long-chain acyl-CoA = an acyl-CoA thioester where the acyl chain contains 23 or more carbon atoms.

Other name(s):

PHS1 (gene name); PAS2 (gene name)

Systematic name:

very-long-chain (3R)-3-hydroxyacyl-CoA hydro-lyase

Comments:

This is the third component of the elongase, a microsomal protein complex responsible for extending palmitoyl-CoA and stearoyl-CoA (and modified forms thereof) to very-long chain acyl CoAs. cf. EC 2.3.1.199, very-long-chain 3-oxoacyl-CoA synthase, EC 1.1.1.330, very-long-chain 3-oxoacyl-CoA reductase, and EC 1.3.1.93, very-long-chain enoyl-CoA reductase.

Links to other databases:

References:

Bach, L., Michaelson, L.V., Haslam, R., Bellec, Y., Gissot, L., Marion, J., Da Costa, M., Boutin, J.P., Miquel, M., Tellier, F., Domergue, F., Markham, J.E., Beaudoin, F., Napier, J.A. and Faure, J.D. The very-long-chain hydroxy fatty acyl-CoA dehydratase PASTICCINO₂ is essential and limiting for plant development. Proc. Natl. Acad. Sci. USA 105 (2008) 14727–14731. [DOI] [PMID: 18799749]

Kihara, A., Sakuraba, H., Ikeda, M., Denpoh, A. and Igarashi, Y. Membrane topology and essential amino acid residues of Phs1, a 3-hydroxyacyl-CoA dehydratase involved in very long-chain fatty acid elongation. J. Biol. Chem. 283 (2008) 11199–11209. [DOI] [PMID: 18272525]

[EC 4.2.1.134 created 2012, modified 2014]

4.2.1.152

Accepted name:

hydroperoxy icosatetraenoate dehydratase

Reaction:

a hydroperoxyicosatetraenoate = an oxoicosatetraenoate + H₂O

Glossary:

(12R)-HPETE = (5Z,8Z,10E,12R,14Z)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
(12S)-HPETE = (5Z,8Z,10E,12S,14Z)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
12-KETE = 12-oxo-ETE = (5Z,8Z,10E,14Z)-12-oxoicosa-5,8,10,14-tetraenoate
(8R)-HPETE = (5Z,8R,9E,11Z,14Z)-8-hydroperoxyicosa-5,9,11,14-tetraenoate
(15R)-HPETE = (5Z,8Z,11Z,13E,15R)-15-hydroperoxyicosa-5,8,11,13-tetraenoate

Other name(s):

epidermal lipoxygenase-3 (ambiguous); eLOX3 (ambiguous)

Systematic name:

hydroperoxyicosatetraenoate hydro-lyase (oxoicosatetraenoate-forming)

Comments:

Binds Fe²⁺. The mammalian enzymes accept a range of hydroperoxyicosatetraenoates (HPETE). The human enzyme has highest activity with (12R)-HPETE, followed by (12S)-HPETE and (15R)-HPETE with much lower efficiency. The murine enzyme has highest activity with (8R)-HPETE followed by (8S)-HPETE. All HPETE isoforms are converted to the corresponding oxoicosatetraenoate forms (KETE) [2]. The enzymes also catalyse the reaction of EC 5.4.4.7, hydroperoxy icosatetraenoate isomerase.

Links to other databases:

References:

1.	Yu, Z., Schneider, C., Boeglin, W.E., Marnett, L.J. and Brash, A.R. The lipoxygenase gene ALOXE3 implicated in skin differentiation encodes a hydroperoxide isomerase. Proc. Natl. Acad. Sci. USA 100 (2003) 9162–9167. [DOI] [PMID: 12881489]
2.	Yu, Z., Schneider, C., Boeglin, W.E. and Brash, A.R. Human and mouse eLOX3 have distinct substrate specificities: implications for their linkage with lipoxygenases in skin. Arch. Biochem. Biophys. 455 (2006) 188–196. [DOI] [PMID: 17045234]
3.	Zheng, Y. and Brash, A.R. Dioxygenase activity of epidermal lipoxygenase-3 unveiled: typical and atypical features of its catalytic activity with natural and synthetic polyunsaturated fatty acids. J. Biol. Chem. 285 (2010) 39866–39875. [DOI] [PMID: 20921226]

[EC 4.2.1.152 created 2014]

4.2.1.153

Accepted name:

3-methylfumaryl-CoA hydratase

Reaction:

(S)-citramalyl-CoA = 3-methylfumaryl-CoA + H₂O

For diagram of the 3-hydroxypropanoate cycle, click here

Glossary:

(S)-citramalyl-CoA = (3S)-3-carboxy-3-hydroxybutanoyl-CoA
3-methylfumaryl-CoA = (E)-3-carboxybut-2-enoyl-CoA

Other name(s):

Meh; mesaconyl-C₄-CoA hydratase; mesaconyl-coenzyme A hydratase (ambiguous)

Systematic name:

(S)-citramalyl-CoA hydro-lyase (3-methylfumaryl-CoA-forming)

Comments:

The enzyme from the bacterium Chloroflexus aurantiacus is part of the 3-hydroxypropanoate cycle for carbon assimilation.

Links to other databases:

References:

1.	Zarzycki, J., Brecht, V., Muller, M. and Fuchs, G. Identifying the missing steps of the autotrophic 3-hydroxypropionate CO₂ fixation cycle in Chloroflexus aurantiacus. Proc. Natl. Acad. Sci. USA 106 (2009) 21317–21322. [DOI] [PMID: 19955419]

[EC 4.2.1.153 created 2014]

4.2.1.154

Accepted name:

tetracenomycin F2 cyclase

Reaction:

tetracenomycin F2 = tetracenomycin F1 + H₂O

For diagram of tetracenomycin biosynthesis, click here

Glossary:

tetracenomycin F1 = 3,8,10,12-tetrahydroxy-1-methyl-11-oxo-6,11-dihydro-2-tetracenecarboxylate = 6,11-dihydro-3,8,10,12-tetrahydroxy-1-methyl-11-oxonaphthacene-2-carboxylate
tetracenomycin F2 = (3E)-4-(3-acetyl-4,5,7-trihydroxy-10-oxo-9,10-dihydroanthracen-2-yl)-3-hydroxybut-3-enoate

Other name(s):

tcmI (gene name)

Systematic name:

tetracenomycin F2 hydro-lyase (tetracenomycin-F1-forming)

Comments:

The enzyme is involved in biosynthesis of the anthracycline antibiotic tetracenomycin C by the bacterium Streptomyces glaucescens.

Links to other databases:

References:

1.	Shen, B. and Hutchinson, C.R. Tetracenomycin F2 cyclase: intramolecular aldol condensation in the biosynthesis of tetracenomycin C in Streptomyces glaucescens. Biochemistry 32 (1993) 11149–11154. [PMID: 8218177]
2.	Thompson, T.B., Katayama, K., Watanabe, K., Hutchinson, C.R. and Rayment, I. Structural and functional analysis of tetracenomycin F2 cyclase from Streptomyces glaucescens. A type II polyketide cyclase. J. Biol. Chem. 279 (2004) 37956–37963. [DOI] [PMID: 15231835]

[EC 4.2.1.154 created 2014]

4.2.3.145

Accepted name:

ophiobolin F synthase

Reaction:

(2E,6E,10E,14E)-geranylfarnesyl diphosphate + H₂O = ophiobolin F + diphosphate

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

Systematic name:

(2E,6E,10E,14E)-geranylfarnesyl-diphosphate diphosphate-lyase (cyclizing, ophiobolin-F-forming)

Comments:

Isolated from the fungus Aspergillus clavatus. The product is a sesterterpenoid (C₂₅ terpenoid).

Links to other databases:

References:

1.	Chiba, R., Minami, A., Gomi, K. and Oikawa, H. Identification of ophiobolin F synthase by a genome mining approach: a sesterterpene synthase from Aspergillus clavatus. Org. Lett. 15 (2013) 594–597. [DOI] [PMID: 23324037]

[EC 4.2.3.145 created 2014]

4.2.3.146

Accepted name:

cyclooctat-9-en-7-ol synthase

Reaction:

geranylgeranyl diphosphate + H₂O = cyclooctat-9-en-7-ol + diphosphate

For diagram of biosynthesis of fusicoccane diterpenoids, click here

Glossary:

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

Other name(s):

cotB2

Systematic name:

geranylgeranyl-diphosphate diphosphate-lyase (cyclooctat-9-en-7-ol-forming)

Comments:

Requires Mg²⁺. Isolated from the bacterium Streptomyces melanosporofaciens, where it is part of the biosynthesis of cyclooctatin, a potent inhibitor of lysophospholipase.

Links to other databases:

References:

1.	Kim, S.Y., Zhao, P., Igarashi, M., Sawa, R., Tomita, T., Nishiyama, M. and Kuzuyama, T. Cloning and heterologous expression of the cyclooctatin biosynthetic gene cluster afford a diterpene cyclase and two P450 hydroxylases. Chem. Biol. 16 (2009) 736–743. [DOI] [PMID: 19635410]
2.	Zhang, X., Shang, G., Gu, L. and Shen, Y. Crystallization and preliminary X-ray diffraction analysis of the diterpene cyclooctatin synthase (CYC) from Streptomyces sp. LZ35. Acta Crystallogr. F Struct. Biol. Commun. 70 (2014) 366–369. [DOI] [PMID: 24598929]
3.	Janke, R., Gorner, C., Hirte, M., Bruck, T. and Loll, B. The first structure of a bacterial diterpene cyclase: CotB2. Acta Crystallogr. D Biol. Crystallogr. 70 (2014) 1528–1537. [DOI] [PMID: 24914964]
4.	Meguro, A., Motoyoshi, Y., Teramoto, K., Ueda, S., Totsuka, Y., Ando, Y., Tomita, T., Kim, S.Y., Kimura, T., Igarashi, M., Sawa, R., Shinada, T., Nishiyama, M. and Kuzuyama, T. An unusual terpene cyclization mechanism involving a carbon-carbon bond rearrangement. Angew. Chem. Int. Ed. Engl. 54 (2015) 4353–4356. [DOI] [PMID: 25689152]
5.	Tomita, T., Kim, S.Y., Teramoto, K., Meguro, A., Ozaki, T., Yoshida, A., Motoyoshi, Y., Mori, N., Ishigami, K., Watanabe, H., Nishiyama, M. and Kuzuyama, T. Structural Insights into the CotB2-catalyzed cyclization of geranylgeranyl diphosphate to the diterpene cyclooctat-9-en-7-ol. ACS Chem. Biol. 12 (2017) 1621–1628. [DOI] [PMID: 28463490]

[EC 4.2.3.146 created 2014]

5.1.3.29

Accepted name:

L-fucose mutarotase

Reaction:

α-L-fucopyranose = β-L-fucopyranose

For diagram of L-fucose catabolism, click here

Other name(s):

FucU; fucose mutarotase; FucM

Systematic name:

L-fucose 1-epimerase

Comments:

This enzyme shows no 1-epimerase activity with D-glucose, L-rhamnose and D-fucose (cf. EC 5.1.3.3, aldose 1-epimerase) [1].

Links to other databases:

References:

1.	Ryu, K.S., Kim, C., Kim, I., Yoo, S., Choi, B.S. and Park, C. NMR application probes a novel and ubiquitous family of enzymes that alter monosaccharide configuration. J. Biol. Chem. 279 (2004) 25544–25548. [DOI] [PMID: 15060078]
2.	Park, D., Ryu, K.S., Choi, D., Kwak, J. and Park, C. Characterization and role of fucose mutarotase in mammalian cells. Glycobiology 17 (2007) 955–962. [DOI] [PMID: 17602138]

[EC 5.1.3.29 created 2014]

5.3.1.31

Accepted name:

sulfoquinovose isomerase

Reaction:

(1) β-sulfoquinovose = 6-deoxy-6-sulfo-D-fructose
(2) β-sulfoquinovose = 6-sulfo-D-rhamnose

For diagram of sulphoglycolysis of sulfoquinovose, click here

Glossary:

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

Other name(s):

yihS (gene name)

Systematic name:

6-deoxy-6-sulfo-β-D-glucopyranose aldose-ketose-isomerase

Comments:

Links to other databases:

References:

1.	Denger, K., Weiss, M., Felux, A.K., Schneider, A., Mayer, C., Spiteller, D., Huhn, T., Cook, A.M. and Schleheck, D. Sulphoglycolysis in Escherichia coli K-12 closes a gap in the biogeochemical sulphur cycle. Nature 507 (2014) 114–117. [DOI] [PMID: 24463506]
2.	Sharma, M., Abayakoon, P., Epa, R., Jin, Y., Lingford, J.P., Shimada, T., Nakano, M., Mui, J.W., Ishihama, A., Goddard-Borger, E.D., Davies, G.J. and Williams, S.J. Molecular basis of sulfosugar selectivity in sulfoglycolysis. ACS Cent. Sci. 7 (2021) 476–487. [DOI] [PMID: 33791429]

[EC 5.3.1.31 created 2014, modified 2022]

*EC

5.4.2.11

Accepted name:

phosphoglycerate mutase (2,3-diphosphoglycerate-dependent)

Reaction:

2-phospho-D-glycerate = 3-phospho-D-glycerate (overall reaction)
(1a) [enzyme]-L-histidine + 2,3-bisphospho-D-glycerate = [enzyme]-N^τ-phospho-L-histidine + 2/3-phospho-D-glycerate
(1b) [enzyme]-N^τ-phospho-L-histidine + 2-phospho-D-glycerate = [enzyme]-L-histidine + 2,3-bisphospho-D-glycerate
(1c) [enzyme]-L-histidine + 2,3-bisphospho-D-glycerate = [enzyme]-N^τ-phospho-L-histidine + 3-phospho-D-glycerate
(1d) [enzyme]-N^τ-phospho-L-histidine + 2/3-bisphospho-D-glycerate = [enzyme]-L-histidine + 2,3-bisphospho-D-glycerate

For diagram of the Entner-Doudoroff pathway, click here

Glossary:

2/3-phospho-D-glycerate = 2-phospho-D-glycerate or 3-phospho-D-glycerate

Other name(s):

glycerate phosphomutase (diphosphoglycerate cofactor); 2,3-diphosphoglycerate dependent phosphoglycerate mutase; cofactor dependent phosphoglycerate mutase; phosphoglycerate phosphomutase (ambiguous); phosphoglyceromutase (ambiguous); monophosphoglycerate mutase (ambiguous); monophosphoglyceromutase (ambiguous); GriP mutase (ambiguous); PGA mutase (ambiguous); MPGM; PGAM; PGAM-d; PGM; dPGM

Systematic name:

D-phosphoglycerate 2,3-phosphomutase (2,3-diphosphoglycerate-dependent)

Comments:

The enzymes from vertebrates, platyhelminths, mollusks, annelids, crustaceans, insects, algae, some fungi and some bacteria (particularly Gram-negative) require 2,3-bisphospho-D-glycerate as a cofactor. The enzyme is activated by 2,3-bisphospho-D-glycerate by transferring a phosphate to histidine (His¹⁰ in man and Escherichia coli, His⁸ in Saccharomyces cerevisiae). This phosphate can be transferred to the free OH of 2-phospho-D-glycerate, followed by transfer of the phosphate already on the phosphoglycerate back to the histidine. cf. EC 5.4.2.12 phosphoglycerate mutase. The enzyme has no requirement for metal ions. This enzyme also catalyse, slowly, the reactions of EC 5.4.2.4 bisphosphoglycerate mutase.

Links to other databases:

References:

1.	Grisolia, S. Phosphoglyceric acid mutase. Methods Enzymol. 5 (1962) 236–242.
2.	Ray, W.J., Jr. and Peck, E.J., Jr. Phosphomutases. In: Boyer, P.D. (Ed.), The Enzymes, 3rd edn, vol. 6, 1972, pp. 407–477.
3.	Rose, Z.B. The enzymology of 2,3-bisphosphoglycerate. Adv. Enzymol. Relat. Areas Mol. Biol. 51 (1980) 211–253. [PMID: 6255773]
4.	Rigden, D.J., Walter, R.A., Phillips, S.E. and Fothergill-Gilmore, L.A. Sulphate ions observed in the 2.12 Å structure of a new crystal form of S. cerevisiae phosphoglycerate mutase provide insights into understanding the catalytic mechanism. J. Mol. Biol. 286 (1999) 1507–1517. [DOI] [PMID: 10064712]
5.	Bond, C.S., White, M.F. and Hunter, W.N. High resolution structure of the phosphohistidine-activated form of Escherichia coli cofactor-dependent phosphoglycerate mutase. J. Biol. Chem. 276 (2001) 3247–3253. [DOI] [PMID: 11038361]
6.	Rigden, D.J., Mello, L.V., Setlow, P. and Jedrzejas, M.J. Structure and mechanism of action of a cofactor-dependent phosphoglycerate mutase homolog from Bacillus stearothermophilus with broad specificity phosphatase activity. J. Mol. Biol. 315 (2002) 1129–1143. [DOI] [PMID: 11827481]
7.	Rigden, D.J., Littlejohn, J.E., Henderson, K. and Jedrzejas, M.J. Structures of phosphate and trivanadate complexes of Bacillus stearothermophilus phosphatase PhoE: structural and functional analysis in the cofactor-dependent phosphoglycerate mutase superfamily. J. Mol. Biol. 325 (2003) 411–420. [DOI] [PMID: 12498792]

[EC 5.4.2.11 created 1961 as EC 5.4.2.1 (EC 2.7.5.3 created 1961, incorporated 1984) transferred 2013 to EC 5.4.2.11, modified 2014]

5.4.4.7

Accepted name:

hydroperoxy icosatetraenoate isomerase

Reaction:

a hydroperoxyicosatetraenoate = a hydroxyepoxyicosatrienoate

Glossary:

(12R)-HPETE = (5Z,8Z,10E,12R,14Z)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
(8S)-HPETE = (5Z,8S,9E,11Z,14Z)-8-hydroperoxyicosa-5,9,11,14-tetraenoate

Other name(s):

epidermal lipoxygenase-3 (ambiguous); eLOX3 (ambiguous)

Systematic name:

hydroperoxyicosatetraenoate hydroxymutase

Comments:

Binds Fe²⁺. The enzyme from mammals accepts a range of hydroperoxyicosatetraenoates producing one or several different hydroxyepoxyicosatrienoates. The human enzyme has highest activity with (12R)-HPETE producing (5Z,8R,9E,11R,12R,14Z)-8-hydroxy-11,12-epoxyicosa-5,9,14-trienoate, followed by (12S)-HPETE producing (5Z,8Z,10R,11S,12S,14Z)-10-hydroxy-11,12-epoxyicosa-5,8,14-trienoate and (5Z,8R,9E,11S,12S,14Z)-8-hydroxy-11,12-epoxyicosa-5,9,14-trienoate [1]. The mouse enzyme has highest activity with (8S)-HPETE, producing (5Z,8S,9S,10R,11Z,14Z)-10-hydroxy-8,9-epoxyicosa-5,11,14-trienoate [2]. The enzymes also have the activity of EC 4.2.1.152, hydroperoxy icosatetraenoate dehydratase.

Links to other databases:

References:

1.	Yu, Z., Schneider, C., Boeglin, W.E., Marnett, L.J. and Brash, A.R. The lipoxygenase gene ALOXE3 implicated in skin differentiation encodes a hydroperoxide isomerase. Proc. Natl. Acad. Sci. USA 100 (2003) 9162–9167. [DOI] [PMID: 12881489]
2.	Yu, Z., Schneider, C., Boeglin, W.E. and Brash, A.R. Human and mouse eLOX3 have distinct substrate specificities: implications for their linkage with lipoxygenases in skin. Arch. Biochem. Biophys. 455 (2006) 188–196. [DOI] [PMID: 17045234]
3.	Zheng, Y. and Brash, A.R. Dioxygenase activity of epidermal lipoxygenase-3 unveiled: typical and atypical features of its catalytic activity with natural and synthetic polyunsaturated fatty acids. J. Biol. Chem. 285 (2010) 39866–39875. [DOI] [PMID: 20921226]

[EC 5.4.4.7 created 2014]

*EC

5.5.1.23

Accepted name:

aklanonic acid methyl ester cyclase

Reaction:

aklaviketone = methyl aklanonate

For diagram of aklavinone biosynthesis, click here

Glossary:

aklaviketone = methyl (1R,2R)-2-ethyl-2,5,7-trihydroxy-4,6,11-trioxo-1,2,3,4,6,11-hexahydrotetracene-1-carboxylate
methyl aklanonate = methyl [4,5-dihydroxy-9,10-dioxo-3-(3-oxopentanoyl)-9,10-dihydroanthracen-2-yl]acetate

Other name(s):

dauD (gene name); aknH (gene name); dnrD (gene name); methyl aklanonate cyclase; methyl aklanonate-aklaviketone isomerase (cyclizing); aklaviketone lyase (decyclizing)

Systematic name:

aklaviketone lyase (ring-opening)

Comments:

The enzyme is involved in the biosynthesis of aklaviketone, an intermediate in the biosynthetic pathways leading to formation of several anthracycline antibiotics, including aclacinomycin, daunorubicin and doxorubicin.

Links to other databases:

References:

1.	Dickens, M.L., Ye, J. and Strohl, W.R. Analysis of clustered genes encoding both early and late steps in daunomycin biosynthesis by Streptomyces sp. strain C5. J. Bacteriol. 177 (1995) 536–543. [DOI] [PMID: 7836284]
2.	Kendrew, S.G., Katayama, K., Deutsch, E., Madduri, K. and Hutchinson, C.R. DnrD cyclase involved in the biosynthesis of doxorubicin: purification and characterization of the recombinant enzyme. Biochemistry 38 (1999) 4794–4799. [DOI] [PMID: 10200167]
3.	Kallio, P., Sultana, A., Niemi, J., Mantsala, P. and Schneider, G. Crystal structure of the polyketide cyclase AknH with bound substrate and product analogue: implications for catalytic mechanism and product stereoselectivity. J. Mol. Biol. 357 (2006) 210–220. [DOI] [PMID: 16414075]

[EC 5.5.1.23 created 2013, modified 2014]

6.1.2.2

Accepted name:

nebramycin 5′ synthase

Reaction:

(1) tobramycin + carbamoyl phosphate + ATP + H₂O = nebramycin 5′ + AMP + diphosphate + phosphate (overall reaction)
(1a) carbamoyl phosphate + ATP + H₂O = diphosphate + O-carbamoyladenylate + phosphate
(1b) O-carbamoyladenylate + tobramycin = AMP + nebramycin 5′
(2) kanamycin A + carbamoyl phosphate + ATP + H₂O = 6′′-O-carbamoylkanamycin A + AMP + diphosphate + phosphate (overall reaction)
(2a) carbamoyl phosphate + ATP + H₂O = diphosphate + O-carbamoyladenylate + phosphate
(2b) O-carbamoyladenylate + kanamycin A = AMP + 6′′-O-carbamoylkanamycin A

For diagram of kanamycin A biosynthesis, click here

Glossary:

tobramycin = (1S,2S,3R,4S,6R)-4,6-diamino-3-(2,6-diamino-2,3,6-trideoxy-α-D-ribo-hexopyranosyloxy)-2-hydroxycyclohexyl 3-amino-3-deoxy-α-D-glucopyranoside
nebramycin 5′ = (1S,2S,3R,4S,6R)-4,6-diamino-3-[(2,6-diamino-2,3,6-trideoxy-α-D-ribo-hexopyranosyl)oxy]-2-hydroxycyclohexyl 3-amino-6-O-carbamoyl-3-deoxy-α-D-glucopyranoside
kanamycin A = (1S,2R,3R,4S,6R)-4,6-diamino-3-(6-amino-6-deoxy^--D-glucopyranosyloxy)-2-hydroxycyclohexyl 3-amino-3-deoxy^--D-glucopyranoside
6′′-O-carbamoylkanamycin A = (1S,2R,3R,4S,6R)-4,6-diamino-3-[(6-amino-6-deoxy-α-D-glucopyranosyl)oxy]-2-hydroxycyclohexyl 3-amino-6-O-carbamoyl-3-deoxy-α-D-glucopyranoside

Other name(s):

tobramycin carbamoyltransferase; TobZ

Systematic name:

tobramycin:carbamoyl phosphate ligase (AMP,phosphate-forming)

Comments:

Requires Fe(III). The enzyme from the bacterium Streptoalloteichus tenebrarius catalyses the activation of carbamoyl phosphate to O-carbamoyladenylate and the subsequent carbamoylation of kanamycin and tobramycin.

Links to other databases:

References:

Parthier, C., Gorlich, S., Jaenecke, F., Breithaupt, C., Brauer, U., Fandrich, U., Clausnitzer, D., Wehmeier, U.F., Bottcher, C., Scheel, D. and Stubbs, M.T. The O-carbamoyltransferase TobZ catalyzes an ancient enzymatic reaction. Angew. Chem. Int. Ed. Engl. 51 (2012) 4046–4052. [DOI] [PMID: 22383337]

[EC 6.1.2.2 created 2014]

6.2.1.41

Accepted name:

3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate—CoA ligase

Reaction:

ATP + 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate + CoA = AMP + diphosphate + 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoyl-CoA

For diagram of cholesterol catabolism, click here

Glossary:

3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate = HIP

Other name(s):

fadD3 (gene name); HIP—CoA ligase

Systematic name:

3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate:CoA ligase (AMP-forming)

Comments:

The enzyme, characterized from actinobacterium Mycobacterium tuberculosis, catalyses a step in the degradation of cholesterol and cholate. The enzyme is very specific for its substrate, and requires that the side chain at C¹⁷ is completely removed.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG

References:

1.	Horinouchi, M., Hayashi, T., Koshino, H. and Kudo, T. ORF18-disrupted mutant of Comamonas testosteroni TA441 accumulates significant amounts of 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oic acid and its derivatives after incubation with steroids. J. Steroid Biochem. Mol. Biol. 101 (2006) 78–84. [DOI] [PMID: 16891113]
2.	Casabon, I., Crowe, A.M., Liu, J. and Eltis, L.D. FadD3 is an acyl-CoA synthetase that initiates catabolism of cholesterol rings C and D in actinobacteria. Mol. Microbiol. 87 (2013) 269–283. [DOI] [PMID: 23146019]

[EC 6.2.1.41 created 2014]

6.2.1.42

Accepted name:

3-oxocholest-4-en-26-oate—CoA ligase

Reaction:

ATP + (25S)-3-oxocholest-4-en-26-oate + CoA = AMP + diphosphate + (25S)-3-oxocholest-4-en-26-oyl-CoA

For diagram of cholic acid biosynthesis (sidechain), click here

Other name(s):

fadD19 (gene name)

Systematic name:

(25S)-3-oxocholest-4-en-26-oate:CoA ligase (AMP-forming)

Comments:

The enzyme, characterized from actinobacterium Mycobacterium tuberculosis, catalyses a step in the degradation of cholesterol. It is responsible for the activation of the C₈ side chain. 3β-hydroxycholest-5-en-26-oate can also be used as substrate.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, KEGG

References:

1.	Wilbrink, M.H., Petrusma, M., Dijkhuizen, L. and van der Geize, R. FadD19 of Rhodococcus rhodochrous DSM43269, a steroid-coenzyme A ligase essential for degradation of C-24 branched sterol side chains. Appl. Environ. Microbiol. 77 (2011) 4455–4464. [DOI] [PMID: 21602385]
2.	Casabon, I., Swain, K., Crowe, A.M., Eltis, L.D. and Mohn, W.W. Actinobacterial acyl coenzyme a synthetases involved in steroid side-chain catabolism. J. Bacteriol. 196 (2014) 579–587. [DOI] [PMID: 24244004]

[EC 6.2.1.42 created 2014]

6.2.1.43

Accepted name:

2-hydroxy-7-methoxy-5-methyl-1-naphthoate—CoA ligase

Reaction:

ATP + 2-hydroxy-7-methoxy-5-methyl-1-naphthoate + CoA = AMP + diphosphate + 2-hydroxy-7-methoxy-5-methyl-1-naphthoyl-CoA

For diagram of neocarzinostatin biosynthesis, click here

Other name(s):

NcsB2

Systematic name:

2-hydroxy-7-methoxy-5-methyl-1-naphthoate:CoA ligase

Comments:

The enzyme from the bacterium Streptomyces carzinostaticus is involved in the attachment of the 2-hydroxy-7-methoxy-5-methyl-1-naphthoate moiety of the antibiotic neocarzinostatin. In vitro the enzyme also catalyses the activation of other 1-naphthoic acid analogues, e.g. 2-hydroxy-5-methyl-1-naphthoate or 2,7-dihydroxy-5-methyl-1-naphthoate.

Links to other databases: