Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB)

Proposed Changes to the Enzyme List

The entries below are proposed additions and amendments to the Enzyme Nomenclature list. The entries below are proposed additions and amendments to the Enzyme Nomenclature list. They were prepared for the NC-IUBMB by Kristian Axelsen, Richard Cammack, Ron Caspi, Masaaki Kotera, Andrew McDonald, Gerry Moss, Dietmar Schomburg, Ida Schomburg and Keith Tipton. Comments and suggestions on these draft entries should be sent to Dr Andrew McDonald (Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland). The date on which an enzyme will be made official is appended after the EC number. To prevent confusion please do not quote new EC numbers until they are incorporated into the main list.

An asterisk before 'EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.


Contents

*EC 1.1.1.203 uronate dehydrogenase (20 January 2015)
EC 1.1.1.379 (R)-mandelate dehydrogenase (20 January 2015)
EC 1.1.1.380 L-gulonate 5-dehydrogenase (20 January 2015)
EC 1.1.1.381 3-hydroxy acid dehydrogenase (20 January 2015)
EC 1.1.3.47 5-(hydroxymethyl)furfural oxidase (20 January 2015)
EC 1.1.4.1 transferred, now EC 1.17.4.4 (20 January 2015)
EC 1.1.4.2 transferred, now EC 1.17.4.5 (20 January 2015)
EC 1.2.1.90 glyceraldehyde-3-phosphate dehydrogenase [NAD(P)+] (20 January 2015)
EC 1.2.1.91 3-oxo-5,6-dehydrosuberyl-CoA semialdehyde dehydrogenase (20 January 2015)
EC 1.2.1.92 3,6-anhydro-α-L-galactose dehydrogenase (20 January 2015)
EC 1.9.98 With other, known, acceptors (20 January 2015)
EC 1.9.98.1 iron—cytochrome-c reductase (20 January 2015)
EC 1.9.99.1 transferred, now EC 1.9.98.1 (20 January 2015)
*EC 1.14.99.42 zeaxanthin 7,8-dioxygenase (20 January 2015)
EC 1.17.1.7 transferred, now EC 1.2.1.91 (20 January 2015)
EC 1.17.4.4 vitamin-K-epoxide reductase (warfarin-sensitive) (20 January 2015)
EC 1.17.4.5 vitamin-K-epoxide reductase (warfarin-insensitive) (20 January 2015)
*EC 1.17.7.1 (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase (ferredoxin) (20 January 2015)
EC 1.17.7.3 (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase (flavodoxin) (20 January 2015)
EC 1.17.98 With other, known, acceptors (20 January 2015)
EC 1.17.98.1 bile-acid 7α-dehydroxylase (20 January 2015)
EC 1.17.99.5 transferred, now EC 1.17.98.1 (20 January 2015)
EC 1.17.99.6 epoxyqueuosine reductase (20 January 2015)
*EC 1.19.6.1 nitrogenase (flavodoxin) (20 January 2015)
EC 1.21.98 With other, known, acceptors (20 January 2015)
EC 1.21.98.1 cyclic dehypoxanthinyl futalosine synthase (20 January 2015)
EC 1.21.99.2 transferred, now EC 1.21.98.1 (20 January 2015)
*EC 2.1.1.192 23S rRNA (adenine2503-C2)-methyltransferase (20 January 2015)
*EC 2.1.1.224 23S rRNA (adenine2503-C8)-methyltransferase (20 January 2015)
EC 2.1.1.308 2-hydroxyethylphosphonate methyltransferase (20 January 2015)
EC 2.1.1.309 18S rRNA (guanine1575-N7)-methyltransferase (20 January 2015)
EC 2.1.1.310 25S rRNA (cytosine2870-C5)-methyltransferase (20 January 2015)
EC 2.1.1.311 25S rRNA (cytosine2278-C5)-methyltransferase (20 January 2015)
EC 2.1.1.312 25S rRNA (uracil2843-N3)-methyltransferase (20 January 2015)
EC 2.1.1.313 25S rRNA (uracil2634-N3)-methyltransferase (20 January 2015)
EC 2.2.1.12 3-acetyloctanal synthase (20 January 2015)
EC 2.3.1.234 N6-L-threonylcarbamoyladenine synthase (20 January 2015)
EC 2.3.1.235 tetracenomycin F2 synthase (20 January 2015)
EC 2.3.1.236 5-methylnaphthoic acid synthase (20 January 2015)
EC 2.3.1.237 neocarzinostatin naphthoate synthase (20 January 2015)
EC 2.3.1.238 monacolin J acid methylbutanoate transferase (20 January 2015)
EC 2.3.1.239 10-deoxymethynolide synthase (20 January 2015)
EC 2.3.1.240 narbonolide synthase (20 January 2015)
EC 2.3.1.241 Kdo2-lipid IVA lauroyltransferase (20 January 2015)
EC 2.3.1.242 Kdo2-lipid IVA palmitoleoyltransferase (20 January 2015)
EC 2.3.1.243 lauroyl-Kdo2-lipid IVA myristoyltransferase (20 January 2015)
EC 2.4.1.332 1,2-α-glucosylglycerol phosphorylase (20 January 2015)
EC 2.4.1.333 1,2-β-oligoglucan phosphorylase (20 January 2015)
EC 2.4.1.334 1,3-α-oligoglucan phosphorylase (20 January 2015)
*EC 2.4.2.54 β-ribofuranosylhydroxybenzene 5'-phosphate synthase (20 January 2015)
*EC 2.5.1.25 tRNA-uridine aminocarboxypropyltransferase (20 January 2015)
EC 2.5.1.128 N4-bis(aminopropyl)spermidine synthase (20 January 2015)
EC 2.6.99.4 transferred, now EC 2.3.1.234 (20 January 2015)
*EC 2.7.7.67 CDP-2,3-bis-(O-geranylgeranyl)-sn-glycerol synthase (20 January 2015)
EC 2.7.8.41 cardiolipin synthase (CMP-forming) (20 January 2015)
*EC 2.8.1.6 biotin synthase (20 January 2015)
*EC 2.8.1.8 lipoyl synthase (20 January 2015)
EC 3.1.1.97 diphthine methylesterase (20 January 2015)
EC 3.1.3.96 pseudouridine 5'-phosphatase (20 January 2015)
EC 3.5.1.27 deleted, covered by EC 3.5.1.88 (20 January 2015)
EC 3.5.2.20 isatin hydrolase (20 January 2015)
*EC 3.5.4.20 pyrithiamine deaminase (20 January 2015)
EC 3.6.1.67 dihydroneopterin triphosphate diphosphatase (20 January 2015)
*EC 4.1.99.19 2-iminoacetate synthase (20 January 2015)
EC 4.2.3.148 cembrene C synthase (20 January 2015)
EC 4.2.3.149 nephthenol synthase (20 January 2015)
EC 4.2.3.150 cembrene A synthase (20 January 2015)
EC 4.2.3.151 pentamethylcyclopentadecatrienol synthase (20 January 2015)
EC 4.4.1.28 L-cysteine desulfidase (20 January 2015)
EC 5.5.1.25 3,6-anhydro-α-L-galactonate cycloisomerase (20 January 2015)
EC 6.3.2.45 UDP-N-acetylmuramate L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptandioate ligase (20 January 2015)
*EC 6.3.4.14 biotin carboxylase (20 January 2015)
EC 6.3.4.24 tyramine—L-glutamate ligase (20 January 2015)

*EC 1.1.1.203

Accepted name: uronate dehydrogenase

Reaction: (1) D-galacturonate + NAD+ = D-galactaro-1,5-lactone + NADH + H+
(2) D-glucuronate + NAD+ = D-glucaro-1,5-lactone + NADH + H+

Other name(s): uronate: NAD-oxidoreductase; uronic acid dehydrogenase

Systematic name: uronate:NAD+ 1-oxidoreductase

Comments: Requires Mg2+. The enzyme, characterized from the bacterium Agrobacterium fabrum, participates in oxidative degradation pathways for galacturonate and glucuronate. The 1,5-lactone product is rather stable at cytosolic pH and does not hydrolyse spontaneously at a substantial rate.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37250-98-9

References:

1. Kilgore, W.W. and Starr, M.P. Uronate oxidation by phytopathogenic pseudomonads. Nature (Lond.) 183 (1959) 1412-1413. [PMID: 13657147]

2. Boer, H., Maaheimo, H., Koivula, A., Penttila, M. and Richard, P. Identification in Agrobacterium tumefaciens of the D-galacturonic acid dehydrogenase gene. Appl. Microbiol. Biotechnol. 86 (2010) 901-909. [PMID: 19921179]

3. Andberg, M., Maaheimo, H., Boer, H., Penttila, M., Koivula, A. and Richard, P. Characterization of a novel Agrobacterium tumefaciens galactarolactone cycloisomerase enzyme for direct conversion of D-galactarolactone to 3-deoxy-2-keto-L-threo-hexarate. J. Biol. Chem. 287 (2012) 17662-17671. [PMID: 22493433]

[EC 1.1.1.203 created 1972 as EC 1.2.1.35, transferred 1984 to EC 1.1.1.203, modified 2014]

EC 1.1.1.379

Accepted name: (R)-mandelate dehydrogenase

Reaction: (R)-mandelate + NAD+ = phenylglyoxylate + NADH + H+

Glossary: (R)-mandelate = D-mandelate

Other name(s): ManDH2; D-ManDH2

Systematic name: (R)-mandelate:NAD+ 2-oxidoreductase

Comments: The enzyme, found in bacteria and fungi, can also accept a number of substituted mandelate derivatives, such as 3-hydroxymandelate, 4-hydroxymandelate, 2-methoxymandelate, 4-hydroxy-3-methoxymandelate and 3-hydroxy-4-methoxymandelate. The enzyme has no activity with (S)-mandelate (cf. EC 1.1.99.31, (S)-mandelate dehydrogenase) [1,2]. The enzyme transfers the pro-R-hydrogen from NADH [2].

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]

3. Wada, Y., Iwai, S., Tamura, Y., Ando, T., Shinoda, T., Arai, K. and Taguchi, H. A new family of D-2-hydroxyacid dehydrogenases that comprises D-mandelate dehydrogenases and 2-ketopantoate reductases. Biosci. Biotechnol. Biochem. 72 (2008) 1087-1094. [PMID: 18391442]

4. Miyanaga, A., Fujisawa, S., Furukawa, N., Arai, K., Nakajima, M. and Taguchi, H. The crystal structure of D-mandelate dehydrogenase reveals its distinct substrate and coenzyme recognition mechanisms from those of 2-ketopantoate reductase. Biochem. Biophys. Res. Commun. 439 (2013) 109-114. [PMID: 23954635]

[EC 1.1.1.379 created 2014]

EC 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.

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. [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. [PMID: 25145794]

[EC 1.1.1.380 created 2014]

EC 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)

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, D-threonine, 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).

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. [PMID: 12535615]

[EC 1.1.1.381 created 2014]

EC 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.

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. [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. [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. [PMID: 24802551]

[EC 1.1.3.47 created 2014]

[EC 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)]

[EC 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)]

EC 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; 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+)].

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. [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. [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. [PMID: 15288789]

[EC 1.2.1.90 created 2014]

EC 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 reaction 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.

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. [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. [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. [PMID: 20660314]

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

EC 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-α-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.

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 (2014) . [PMID: 25156229]

[EC 1.2.1.92 created 2014]

EC 1.9.98 With other, known, acceptors

EC 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.

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]

[EC 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

Accepted name: zeaxanthin 7,8-dioxygenase

Reaction: zeaxanthin + 2 O2 = crocetin dialdehyde + 2 (3S)-3-hydroxycyclocitral (overall reaction)
(1a) zeaxanthin + O2 = β-citraurin + (3S)-3-hydroxycyclocitral
(1b) β-citraurin + O2 = crocetin dialdehyde + (3S)-3-hydroxycyclocitral

For diagram of reaction click here.

Glossary: β-citraurin = 3-hydroxy-β-apo-8'-carotenal

Other name(s): zeaxanthin 7,8(7',8')-cleavage dioxygenase; CsZCD (incorrect); CCD2 (gene name)

Systematic name: zeaxanthin:oxygen oxidoreductase (7,8-cleaving)

Comments: The enzyme, characterized from the plant Crocus sativus, acts twice on zeaxanthin, cleaving 3-hydroxycyclocitral off each 3-hydroxy end group. It is part of the zeaxanthin degradation pathway in that organism, leading to the different compounds that impart the color, flavor and aroma of the saffron spice.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Frusciante, S., Diretto, G., Bruno, M., Ferrante, P., Pietrella, M., Prado-Cabrero, A., Rubio-Moraga, A., Beyer, P., Gomez-Gomez, L., Al-Babili, S. and Giuliano, G. Novel carotenoid cleavage dioxygenase catalyzes the first dedicated step in saffron crocin biosynthesis. Proc. Natl. Acad. Sci. USA 111 (2014) 12246-12251. [PMID: 25097262]

[EC 1.14.99.42 created 2011, modified 2014]

[EC 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)]

EC 1.17.4.4

Accepted name: vitamin-K-epoxide reductase (warfarin-sensitive)

Reaction: phylloquinone + oxidized dithiothreitol + H2O = 2,3-epoxy-2-methyl-3-phytyl-2,3-dihydro-1,4-naphthoquinone + 1,4-dithiothreitol

For diagram of reaction click here.

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

Systematic name: phylloquinone:oxidized-dithiothreitol oxidoreductase

Comments: Vitamin K 2,3-epoxide is reduced to vitamin K and possibly to vitamin K hydroquinone by 1,4-dithiothreitol, which is oxidized to a disulfide; some other dithiols and 4-butanethiol can also act. Inhibited strongly by warfarin [cf. EC 1.17.4.5, vitamin-K-epoxide reductase (warfarin-insensitive)].

References:

1. 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]

2. 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. [PMID: 3857611]

3. 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]

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

EC 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)].

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. [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 reaction 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 [3]. 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: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:

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. [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. [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. [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. [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]

EC 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 reaction 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); ispG (gene name)

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. Plants and cyanobacteria have a similar enzyme that utilizes ferredoxin rather than flavodoxin (cf. EC 1.17.7.1).

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. [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. [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. [PMID: 15978585]

[EC 1.17.7.3 created 2014]

EC 1.17.98 With other, known, acceptors

EC 1.17.98.1

Accepted name: bile-acid 7α-dehydroxylase

Reaction: (1) deoxycholate + FAD + H2O = cholate + FADH2
(2) lithocholate + FAD + H2O = chenodeoxycholate + FADH2

For diagram of reaction click here and of proposed mechanism, click here.

Glossary: cholate = 3α,7α,12α-trihydroxy-5β-cholan-24-oate
deoxycholate = 3α,12α-dihydroxy-5β-cholan-24-oate
lithocholate = 3α-hydroxy-5β-cholan-24-oate
chenodeoxycholate = 3α,7α-dihydroxy-5β-cholan-24-oate
allodeoxycholate = 3α,12α-dihydroxy-5α-cholan-24-oate

Other name(s): cholate 7α-dehydroxylase; 7α-dehydroxylase; bile acid 7-dehydroxylase; deoxycholate:NAD+ oxidoreductase

Systematic name: deoxycholate:FAD oxidoreductase (7α-dehydroxylating)

Comments: Under physiological conditions, the reactions form deoxycholate. This enzyme is highly specific for bile-acid substrates and requires a free C-24 carboxy group and an unhindered 7α-hydroxy group on the B-ring of the steroid nucleus for activity, as found in cholate and chenodeoxycholate. The reaction is stimulated by the presence of NAD+ but is inhibited by excess NADH. This unusual regulation by the NAD+/NADH ratio is most likely the result of the intermediates being linked at C-24 by an anhydride bond to the 5'-diphosphate of 3'-phospho-ADP [2,5,6]. Allodeoxycholate is also formed as a side-product of the 7α-dehydroxylation of cholate [6]. The enzyme is present in intestinal anaerobic bacteria [6], even though its products are important in mammalian physiology.

References:

1. White, B.A., Cacciapuoti, A.F., Fricke, R.J., Whitehead, T.R., Mosbach, E.H. and Hylemon, P.B. Cofactor requirements for 7α-dehydroxylation of cholic and chenodeoxycholic acid in cell extracts of the intestinal anaerobic bacterium, Eubacterium species V.P.I. 12708. J. Lipid Res. 22 (1981) 891-898. [PMID: 7276750]

2. White, B.A., Paone, D.A., Cacciapuoti, A.F., Fricke, R.J., Mosbach, E.H. and Hylemon, P.B. Regulation of bile acid 7-dehydroxylase activity by NAD+ and NADH in cell extracts of Eubacterium species V.P.I. 12708. J. Lipid Res. 24 (1983) 20-27. [PMID: 6833878]

3. Coleman, J.P., White, W.B. and Hylemon, P.B. Molecular cloning of bile acid 7-dehydroxylase from Eubacterium sp. strain VPI 12708. J. Bacteriol. 169 (1987) 1516-1521. [PMID: 3549693]

4. Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137-174. [PMID: 12543708]

5. Coleman, J.P., White, W.B., Egestad, B., Sjövall, J. and Hylemon, P.B. Biosynthesis of a novel bile acid nucleotide and mechanism of 7α-dehydroxylation by an intestinal Eubacterium species. J. Biol. Chem. 262 (1987) 4701-4707. [PMID: 3558364]

6. Hylemon, P.B., Melone, P.D., Franklund, C.V., Lund, E. and Björkhem, I. Mechanism of intestinal 7α-dehydroxylation of cholic acid: evidence that allo-deoxycholic acid is an inducible side-product. J. Lipid Res. 32 (1991) 89-96. [PMID: 2010697]

[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]

[EC 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)]

EC 1.17.99.6

Accepted name: epoxyqueuosine reductase

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

For diagram of reaction 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

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.

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. [PMID: 21502530]

[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, KEGG, MetaCyc, 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]

EC 1.21.98 With other, known, acceptors

EC 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 reaction 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.

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. [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. [PMID: 23763543]

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

[EC 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: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

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. [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. [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. [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. [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. [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 SN2 displacement and radical generation. J. Am. Chem. Soc. 133 (2011) 19586-19589. [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. [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. [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. [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-S] cluster [1]. 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. RlmN 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: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

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. [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. [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. [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. [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. [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. [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 SN2 displacement and radical generation. J. Am. Chem. Soc. 133 (2011) 19586-19589. [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. [PMID: 23644479]

[EC 2.1.1.224 created 2011, modified 2014]

EC 2.1.1.308

Accepted name: 2-hydroxyethylphosphonate methyltransferase

Reaction: S-adenosyl-L-methionine + methylcob(III)alamin + 2-hydroxyethylphosphonate = 5'-deoxyadenosine + L-methionine + cob(III)alamin + (2S)-2-hydroxypropylphosphonate

For diagram of reaction click here.

Other name(s): Fom3

Systematic name: S-adenosyl-L-methionine:methylcob(III)alamin:2-hydroxyethylphosphonate methyltransferase

Comments: Requires cobalamin. The enzyme, isolated from the bacterium Streptomyces wedmorensis, is a member of the ‘AdoMet radical’ (radical SAM) family. Involved in fosfomycin biosynthesis.

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. [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. [PMID: 24370735]

[EC 2.1.1.308 created 2014]

EC 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].

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. [PMID: 18332120]

[EC 2.1.1.309 created 2014]

EC 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].

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. [PMID: 23913415]

[EC 2.1.1.310 created 2014]

EC 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].

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. [PMID: 23913415]

[EC 2.1.1.311 created 2014]

EC 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.

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. [PMID: 24335083]

[EC 2.1.1.312 created 2014]

EC 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.

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. [PMID: 24335083]

[EC 2.1.1.313 created 2014]

EC 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.

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. [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. [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. [PMID: 24957249]

[EC 2.2.1.12 created 2014]

EC 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 reaction 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. tRNAIle, tRNAThr, tRNAAsn, tRNALys, tRNASer and tRNAArg [3].

References:

1. Lauhon, C.T. Mechanism of N6-threonylcarbamoyladenonsine (t6A) biosynthesis: isolation and characterization of the intermediate threonylcarbamoyl-AMP. Biochemistry 51 (2012) 8950-8963. [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. [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. [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. [PMID: 23620299]

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

EC 2.3.1.235

Accepted name: tetracenomycin F2 synthase

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

For diagram of reaction 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.

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. [PMID: 9609708]

[EC 2.3.1.235 created 2014]

EC 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 reaction 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.

References:

1. 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. [PMID: 18635006]

[EC 2.3.1.236 created 2014]

EC 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 reaction 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.

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. [PMID: 15147895]

[EC 2.3.1.237 created 2014]

EC 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 reaction 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.

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. [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. [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. [PMID: 19530726]

[EC 2.3.1.238 created 2014]

EC 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 reaction 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.

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. [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. [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. [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. [PMID: 24965656]

[EC 2.3.1.239 created 2014]

EC 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 reaction 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.

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. [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. [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. [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. [PMID: 24965656]

[EC 2.3.1.240 created 2014]

EC 2.3.1.241

Accepted name: Kdo2-lipid IVA lauroyltransferase

Reaction: a dodecanoyl-[acyl-carrier protein] + Kdo2-lipid IVA = dodecanoyl-Kdo2-lipid IVA + an [acyl-carrier protein]

For diagram of reaction click here.

Glossary: Kdo = 3-deoxy-D-manno-oct-2-ulopyranosylonic acid
lipid IVA = 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 IVA = α-Kdo-(2→4)-α-Kdo-(2→6)-lipid IVA
dodecanoyl = lauroyl
dodecanoyl-Kdo2-lipid IVA = α-Kdo-(2→4)-α-Kdo-(2→6)-2-deoxy-2-[(3R)-3-(dodecanoyloxy)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): LpxL; htrB (gene name); dodecanoyl-[acyl-carrier protein]:α-Kdo-(2→4)-α-Kdo-(2→6)-lipid IVA O-dodecanoyltransferase; lauroyl-[acyl-carrier protein]:Kdo2-lipid IVA O-lauroyltransferase; (Kdo)2-lipid IVA lauroyltransferase; α-Kdo-(2→4)-α-(2→6)-lipid IVA lauroyltransferase

Systematic name: dodecanoyl-[acyl-carrier protein]:Kdo2-lipid IVA O-dodecanoyltransferase

Comments: The enzyme, characterized from the bacterium Escherichia coli, is involved in the biosynthesis of the phosphorylated outer membrane glycolipid lipid A.

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. [PMID: 8662613]

2. 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. [PMID: 18656959]

[EC 2.3.1.241 created 2014]

EC 2.3.1.242

Accepted name: Kdo2-lipid IVA palmitoleoyltransferase

Reaction: a (9Z)-hexadec-9-enoyl-[acyl-carrier protein] + Kdo2-lipid IVA = (9Z)-hexadec-9-enoyloxy-Kdo2-lipid IVA + an [acyl-carrier protein]

For diagram of reaction click here.

Glossary: Kdo = 3-deoxy-D-manno-oct-2-ulopyranosylonic acid
lipid IVA = 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 IVA = α-Kdo-(2→4)-α-Kdo-(2→6)-lipid IVA
(9Z)-hexadec-9-enoyl = palmitoleoyl
(9Z)-hexadec-9-enoyloxy-Kdo2-lipid IVA = α-Kdo-(2→4)-α-Kdo-(2→6)-2-deoxy-2-{(3R)-3-[(9Z)-hexadec-9-enoyloxy]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 IVA O-palmitoleoyltransferase; (Kdo)2-lipid IVA palmitoleoyltransferase; α-Kdo-(2→4)-α-(2→6)-lipid IVA palmitoleoyltransferase

Systematic name: (9Z)-hexadec-9-enoyl-[acyl-carrier protein]:α-Kdo-(2→4)-α-Kdo-(2→6)-lipid IVA 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.

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. [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. [PMID: 11830594]

[EC 2.3.1.242 created 2014]

EC 2.3.1.243

Accepted name: lauroyl-Kdo2-lipid IVA myristoyltransferase

Reaction: a tetradecanoyl-[acyl-carrier protein] + dodecanoyl-Kdo2-lipid IVA = dodecanoyl-(tetradecanoyl)-Kdo2-lipid IVA + an [acyl-carrier protein]

For diagram of reaction click here.

Glossary: Kdo = 3-deoxy-D-manno-oct-2-ulopyranosylonic acid
lipid IVA = 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 IVA = α-Kdo-(2→4)-α-Kdo-(2→6)-lipid IVA
dodecanoyl = lauroyl
tetradecanoyl = myristoyl
dodecanoyl-Kdo2-lipid IVA = α-Kdo-(2→4)-α-Kdo-(2→6)-2-deoxy-2-[(3R)-3-(dodecanoyloxy)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
dodecanoyl-(tetradecanoyl)-Kdo2-lipid IVA = α-Kdo-(2→4)-α-Kdo-(2→6)-2-deoxy-2-[(3R)-3-(dodecanoyloxy)tetradecanamido]-3-O-[(3R)-3-(tetradecanoyloxy)tetradecanoyl]-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): MsbB acyltransferase; lpxM (gene name); myristoyl-[acyl-carrier protein]:α-Kdo-(2→4)-α-Kdo-(2→6)-(dodecanoyl)-lipid IVA O-myristoyltransferase

Systematic name: tetradecanoyl-[acyl-carrier protein]:dodecanoyl-Kdo2-lipid IVA O-tetradecanoyltransferase

Comments: The enzyme, characterized from the bacterium Escherichia coli, is involved in the biosynthesis of the phosphorylated outer membrane glycolipid lipid A.

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. [PMID: 9099672]

[EC 2.3.1.243 created 2014]

EC 2.4.1.332

Accepted name: 1,2-α-glucosylglycerol phosphorylase

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

Other name(s): 2-O-α-D-glucopyranosylglycerol phosphorylase

Systematic name: 2-O-α-D-glucopyranosyl-sn-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.

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 (2014) e86548. [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. [PMID: 24828502]

[EC 2.4.1.332 created 2014]

EC 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.

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 (2014) e92353. [PMID: 24647662]

[EC 2.4.1.333 created 2014]

EC 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).

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-ribofuranosylhydroxybenzene 5'-phosphate synthase

Reaction: 5-phospho-α-D-ribose 1-diphosphate + 4-hydroxybenzoate = 4-(β-D-ribofuranosyl)hydroxybenzene 5'-phosphate + diphosphate

For diagram of reaction click here.

Other name(s): β-RFAP synthase (incorrect); β-RFA-P synthase (incorrect); AF2089 (gene name); MJ1427 (gene name); 4-(β-D-ribofuranosyl)aminobenzene 5'-phosphate synthase (incorrect); β-ribofuranosylaminobenzene 5'-phosphate synthase (incorrect)

Systematic name: 5-phospho-α-D-ribose 1-diphosphate:4-aminobenzoate 5-phospho-β-D-ribofuranosyltransferase (decarboxylating)

Comments: The enzyme is involved in biosynthesis of tetrahydromethanopterin in archaea. It was initially thought to use 4-aminobenzoate as a substrate, but was later shown to utilize 4-hydroxybenzoate [4]. The activity is dependent on Mg2+ or Mn2+ [1].

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

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. [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. [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. [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. [PMID: 21634403]

[EC 2.4.2.54 created 2013, modified 2014]

*EC 2.5.1.25

Accepted name: tRNA-uridine aminocarboxypropyltransferase

Reaction: S-adenosyl-L-methionine + uridine47 tRNAPhe = S-methyl-5'-thioadenosine + 3-[(3S)-3-amino-3-carboxypropyl]-uridine47 in tRNAPhe

Other name(s): S-adenosyl-L-methionine:tRNA-uridine 3-(3-amino-3-carboxypropyl)transferase

Systematic name: S-adenosyl-L-methionine:uridine47 in tRNAPhe 3-[(3S)-3-amino-3-carboxypropyl]transferase

Comments: The enzyme was studied in the bacterium Escherichia coli. The modification is found in the variable loop of the tRNA.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

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. [PMID: 4597321]

[EC 2.5.1.25 created 1984, modified 2014]

EC 2.5.1.128

Accepted name: N4-bis(aminopropyl)spermidine synthase

Reaction: 2 S-adenosyl 3-(methylthio)propylamine + spermidine = 2 S-methyl-5'-thioadenosine + N4-bis(aminopropyl)spermidine (overall reaction)
(1a) S-adenosyl 3-(methylthio)propylamine + spermidine = S-methyl-5'-thioadenosine + N4-aminopropylspermidine
(1b) S-adenosyl 3-(methylthio)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-(methylthio)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.

References:

1. 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. [PMID: 24610711]

[EC 2.5.1.128 created 2014]

[EC 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 reaction 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): 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, KEGG, MetaCyc, 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. [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. [PMID: 12562787]

[EC 2.7.7.67 created 2009, modified 2014]

EC 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.

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. [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. [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. [PMID: 19439403]

5. Sarma, P.V., Srikanth, L., Venkatesh, K., Murthy, P.S. and Sarma, P.U. Isolation, purification and characterization of cardiolipin synthase from Mycobacterium phlei. Bioinformation 9 (2013) 690-695. [PMID: 23930021]

[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

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, each producing 5'-deoxyadenosine and a putative dethiobiotinyl carbon radical. Reaction with another equivalent of AdoMet results in abstraction of the C6 methylene pro-S hydrogen atom from 9-mercaptodethiobiotin, and the resulting carbon radical is quenched via formation of an intramolecular C-S bond, thus closing the biotin thiophane 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, KEGG, MetaCyc, 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. [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. [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. [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. [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. [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. [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. [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)lysine + 2 sulfur-(sulfur carrier) + 2 S-adenosyl-L-methionine + 2 reduced [2Fe-2S] ferredoxin = protein N6-(lipoyl)lysine + 2 (sulfur carrier) + 2 L-methionine + 2 5'-deoxyadenosine + 2 oxidized [2Fe-2S] ferredoxin

Other name(s): LS; LipA; lipoate synthase; protein 6-N-(octanoyl)lysine:sulfur sulfurtransferase; protein N6-(octanoyl)lysine:sulfur sulfurtransferase

Systematic name: protein N6-(octanoyl)lysine:sulfur-(sulfur carrier) sulfurtransferase

Comments: This enzyme 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 [i.e. S-adenosylmethionine, or S-(5'-deoxyadenosin-5'-yl)methionine], by the addition of an electron from an iron-sulfur centre. The radical is converted into 5'-deoxyadenosine when it abstracts a hydrogen atom from C-6 and C-8, leaving reactive radicals at these positions so that they can add sulfur, with inversion of configuration [4]. This enzyme catalyses the final step in the de-novo biosynthesis of the lipoyl cofactor, with the other enzyme involved being EC 2.3.1.181, lipoyl(octanoyl) transferase. 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) [2,5]. An alternative lipoylation pathway involves EC 2.7.7.63, lipoate—protein ligase, which can lipoylate apoproteins using exogenous lipoic acid (or its analogues) [7].

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, 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. [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. [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. [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. [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. [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. [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. [PMID: 10966480]

[EC 2.8.1.8 created 2006, modified 2014]

EC 3.1.1.97

Accepted name: diphthine methylesterase

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

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

Systematic name: diphthine methyl ester acylhydrolase

Comments: The protein is only present in eukaryotes.

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. [PMID: 24739148]

[EC 3.1.1.97 created 2014]

EC 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.

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. [PMID: 20722631]

[EC 3.1.3.96 created 2014]

[EC 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)]

EC 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.

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. [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-(2-hydroxyethyl)-2-methylpyridinium-bromide aminohydrolase

Systematic name: 1-(4-amino-2-methylpyrimid-5-ylmethyl)-3-(β-hydroxyethyl)-2-methylpyridinium aminohydrolase

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, 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]

EC 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+.

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. [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. [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. [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 reaction 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: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

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. [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. [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. [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. [PMID: 19923213]

[EC 4.1.99.19 created 2011, modified 2014]

EC 4.2.3.148

Accepted name: cembrene C synthase

Reaction: geranylgeranyl diphosphate = cembrene C + diphosphate

For diagram of reaction 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.

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. [PMID: 23386483]

[EC 4.2.3.148 created 2014]

EC 4.2.3.149

Accepted name: nephthenol synthase

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

For diagram of reaction 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).

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. [PMID: 23386483]

[EC 4.2.3.149 created 2014]

EC 4.2.3.150

Accepted name: cembrene A synthase

Reaction: geranylgeranyl diphosphate = (R)-cembrene A + diphosphate

For diagram of reaction 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.

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. [PMID: 23386483]

[EC 4.2.3.150 created 2014]

EC 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 reaction 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.

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. [PMID: 23386483]

[EC 4.2.3.151 created 2014]

EC 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 bound 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).

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. [PMID: 15683250]

[EC 4.4.1.28 created 2014]

EC 5.5.1.25

Accepted name: 3,6-anhydro-α-L-galactonate cycloisomerase

Reaction: 3,6-anhydro-α-L-galactonate = 2-dehydro-3-deoxy-D-galactonate

Systematic name: 3,6-anhydro-α-L-galactonate lyase (ring-opening)

Comments: The enzyme, characterized from the marine bacterium Vibrio sp. EJY3, is involved in a degradation pathway for 3,6-anhydro-α-L-galactopyranose, a major component of the polysaccharides of red macroalgae.

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 (2014) . [PMID: 25156229]

[EC 5.5.1.25 created 2014]

EC 6.3.2.45

Accepted name: UDP-N-acetylmuramate L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptandioate 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-diaminoheptandioate ligase

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-diaminoheptandioyl-D-alanyl-D-alanine in vivo and in vitro. Requires Mg2+.

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. [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. [PMID: 17384195]

[EC 6.3.2.45 created 2014]

*EC 6.3.4.14

Accepted name: biotin carboxylase

Reaction: ATP + biotin-carboxyl-carrier protein + hydrogen carbonate = ADP + phosphate + carboxybiotin-carboxyl-carrier protein

Other name(s): biotin carboxylase (component of acetyl CoA carboxylase)

Systematic name: biotin-carboxyl-carrier-protein:carbon-dioxide ligase (ADP-forming)

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, 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. [PMID: 4922289]

[EC 6.3.4.14 created 1976, modified 2014]

EC 6.3.4.24

Accepted name: tyramine—L-glutamate ligase

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

Other name(s): mfnD (gene name)

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

Comments: The enzyme, which has been characterized from the archaebacterium 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+.

References:

1. Wang, Y., Xu, H., Harich, K.C. and White, R.H. Identification and characterization of a tyramine-glutamate ligase (MfnD) Involved in methanofuran biosynthesis. Biochemistry 53 (2014) 6220-6230. [PMID: 25211225]

[EC 6.3.4.24 created 2014]


Return to enzymes home page.