An asterisk before "EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.
Accepted name: trans-4-hydroxycyclohexanecarboxylate dehydrogenase
Reaction: trans-4-hydroxycyclohexane-1-carboxylate + NAD+ = 4-oxocyclohexane-1-carboxylate + NADH + H+
Glossary: trans-4-hydroxycyclohexane-1-carboxylate = trans-4-hydroxycyclohexanecarboxylate
4-oxocyclohexane-1-carboxylate = 4-oxocyclohexanecarboxylate
Other name(s): 4-hydroxycyclohexanecarboxylate dehydrogenase (ambiguous); chcB1 (gene name)
Systematic name: trans-4-hydroxycyclohexane-1-carboxylate:NAD+ 4-oxidoreductase
Comments: The enzyme from Corynebacterium cyclohexanicum is highly specific for the trans-4-hydroxy derivative. cf. EC 1.1.1.438, cis-4-hydroxycyclohexanecarboxylate dehydrogenase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 67272-36-0
References:
1. Obata, H., Uebayashi, M. and Kaneda, T. Purification and properties of 4-hydroxycyclohexanecarboxylate dehydrogenase from Corynebacterium cyclohexanicum. Eur. J. Biochem. 174 (1988) 451-458. [PMID: 3292236]
2. Yamamoto, T., Hasegawa, Y., Lau, P.CK. and Iwaki, H. Identification and characterization of a chc gene cluster responsible for the aromatization pathway of cyclohexanecarboxylate degradation in Sinomonas cyclohexanicum ATCC 51369. J. Biosci. Bioeng. 132 (2021) 621-629. [PMID: 34583900]
Accepted name: cis-4-hydroxycyclohexanecarboxylate dehydrogenase
Reaction: cis-4-hydroxycyclohexane-1-carboxylate + NAD+ = 4-oxocyclohexane-1-carboxylate + NADH + H+
Glossary: cis-4-hydroxycyclohexane-1-carboxylate = cis-4-hydroxycyclohexanecarboxylate
4-oxocyclohexane-1-carboxylate = 4-oxocyclohexanecarboxylate
Other name(s): chcB2 (gene name)
Systematic name: cis-4-hydroxycyclohexane-1-carboxylate:NAD+ 4-oxidoreductase
Comments: The enzyme from Corynebacterium cyclohexanicum is highly specific for the cis-4-hydroxy derivative. cf. EC 1.1.1.226, trans-4-hydroxycyclohexanecarboxylate dehydrogenase
References:
1. Yamamoto, T., Hasegawa, Y., Lau, P.CK. and Iwaki, H. Identification and characterization of a chc gene cluster responsible for the aromatization pathway of cyclohexanecarboxylate degradation in Sinomonas cyclohexanicum ATCC 51369. J. Biosci. Bioeng. 132 (2021) 621-629. [PMID: 34583900]
Accepted name: carboxyaminopropylagmatine dehydrogenase
Reaction: N1-[(S)-3-amino-3-carboxypropyl]agamatine + NADP+ + H2O = agmatine + L-aspartate 4-semialdehyde + NADPH + H+
Glossary: N1-[(S)-3-amino-3-carboxypropyl]agamatine = carboxyaminopropylagmatine
L-aspartate 4-semialdehyde = L-aspartate β-semialdehyde
Other name(s): slr0049 (locus name)
Systematic name: N1-[(S)-2-aminobutanoate]agmatine:NADP+ oxidoreductase (agmatine-forming)
Comments: The enzyme, characterized from the cyanobacterium Synechocystis sp. PCC 6803, catalyses the reductive condensation of agmatine and L-aspartate 4-semialdehyde. It participates in a biosynthetic pathway for spermidine.
References:
1. Xi, H., Nie, X., Gao, F., Liang, X., Li, H., Zhou, H., Cai, Y. and Yang, C. A bacterial spermidine biosynthetic pathway via carboxyaminopropylagmatine. Sci Adv 9 (2023) eadj9075. [PMID: 37878710]
Accepted name: putrescine N-hydroxylase
Reaction: putrescine + NADPH + H+ + O2 = N-hydroxyputrescine + NADP+ + H2O
For diagram of reaction click here
Other name(s): alcA (gene name); pubA (gene name); fbsI (gene name)
Systematic name: putrescine,NADPH:oxygen oxidoreductase (N-hydroxylating)
Comments: Contains FAD. The enzyme, characterized from multiple bacterial species, participates in the biosynthesis of assorted siderophores.
References:
1. Kadi, N., Arbache, S., Song, L., Oves-Costales, D. and Challis, G.L. Identification of a gene cluster that directs putrebactin biosynthesis in Shewanella species: PubC catalyzes cyclodimerization of N-hydroxy-N-succinylputrescine. J. Am. Chem. Soc. 130 (2008) 10458-10459. [PMID: 18630910]
2. Li, B., Lowe-Power, T., Kurihara, S., Gonzales, S., Naidoo, J., MacMillan, J.B., Allen, C. and Michael, A.J. Functional identification of putrescine C- and N-hydroxylases. ACS Chem. Biol. 11 (2016) 2782-2789. [PMID: 27541336]
3. Lyons, N.S., Bogner, A.N., Tanner, J.J. and Sobrado, P. Kinetic and structural characterization of a flavin-dependent putrescine N-hydroxylase from Acinetobacter baumannii. Biochemistry 61 (2022) 2607-2620. [PMID: 36314559]
Accepted name: taxane 9α-hydroxylase
Reaction: 5,20-epoxytax-11-en-4α-ol + [reduced NADPH—hemoprotein reductase] + O2 = 5,20-epoxytax-11-ene-4α,9α-diol + [oxidized NADPH—hemoprotein reductase] + H2O
Other name(s): taxoid 9α hydroxylase; CYP725A22; T9αOH
Systematic name: 5,20-epoxytax-11-en-4α-ol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (9α-hydroxylating)
Comments: The enzyme is active in the biosynthetic pathway of paclitaxel (Taxol) in Taxus species (yew)
References:
1. Zhang, Y., Wiese, L., Fang, H., Alseekh, S., Perez de Souza, L., Scossa, F., Molloy, J., Christmann, M. and Fernie, A.R. Synthetic biology identifies the minimal gene set required for paclitaxel biosynthesis in a plant chassis. Mol. Plant 16 (2023) 1951-1961. [PMID: 37897038]
Accepted name: 4-oxocyclohexanecarboxylate 2-dehydrogenase
Reaction: 4-oxocyclohexane-1-carboxylate + O2 = 4-oxocyclohex-2-ene-1-carboxylate + H2O2
Glossary: 4-oxocyclohexane-1-carboxylate = 4-oxocyclohexanecarboxylate
Other name(s): chcC1 (gene name); 4-oxocyclohexanecarboxylate desaturase I; 4-oxocyclohexanecarboxylate 2-desaturase
Systematic name: 4-oxocyclohexane-1-carboxylate:oxygen oxidoreductase (4-oxocyclohex-2-ene-1-carboxylate-forming)
Comments: Contains FAD. The enzyme, characterized from the bacterium Corynebacterium cyclohexanicum, participates in a cyclohexane-1-carboxylate degradation pathway.
References:
1. Kaneda, T., Obata, H. and Tokumoto, M. Aromatization of 4-oxocyclohexanecarboxylic acid to 4-hydroxybenzoic acid by two distinctive desaturases from Corynebacterium cyclohexanicum. Properties of two desaturases. Eur. J. Biochem. 218 (1993) 997-1003. [PMID: 8281951]
2. Yamamoto, T., Hasegawa, Y., Lau, P.CK. and Iwaki, H. Identification and characterization of a chc gene cluster responsible for the aromatization pathway of cyclohexanecarboxylate degradation in Sinomonas cyclohexanicum ATCC 51369. J. Biosci. Bioeng. 132 (2021) 621-629. [PMID: 34583900]
[EC 2.1.1.86 Transferred entry: tetrahydromethanopterin S-methyltransferase. Now EC 7.2.1.4, tetrahydromethanopterin S-methyltransferase (EC 2.1.1.86 created 1989, modified 2000, modified 2017, deleted 2024)]
Accepted name: 5-guanidino-2-oxopentanoate (3R)-methyltransferase
Reaction: S-adenosyl-L-methionine + 5-guanidino-2-oxopentanoate = S-adenosyl-L-homocysteine + (3R)-5-guanidino-3-methyl-2-oxopentanoate
Glossary: 5-guanidino-2-oxopentanoate = 2-ketoarginine
(3R)-5-guanidino-3-methyl-2-oxopentanoate = (3R)-5-carbamimidamido-3-methyl-2-oxopentanoate
Other name(s): mrsA (gene name); argN (gene name); 2-ketoarginine methyltransferase; S-adenosyl-L-methionine:5-carbamimidamido-2-oxopentanoate S-methyltransferase
Systematic name: S-adenosyl-L-methionine:5-guanidino-2-oxopentanoate (3R)-methyltransferase
Comments: The enzyme is involved in production of the rare amino acid (3R)-3-methyl-L-arginine. The compound is used by the epiphytic bacterium Pseudomonas syringae pv. syringae as an antibiotic against the related pathogenic species Pseudomonas savastanoi pv. glycinea. Other bacteria incorporate the compound into more complex compounds such as the peptidyl nucleoside antibiotic arginomycin.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc,
References:
1. Braun, S.D., Hofmann, J., Wensing, A., Ullrich, M.S., Weingart, H., Völksch, B. and Spiteller, D. Identification of the biosynthetic gene cluster for 3-methylarginine, a toxin produced by Pseudomonas syringae pv. syringae 22d/93. Appl. Environ. Microbiol. 76 (2010) 2500-2508. [PMID: 20190091]
2. Feng, J., Wu, J., Gao, J., Xia, Z., Deng, Z. and He, X. Biosynthesis of the β-methylarginine residue of peptidyl nucleoside arginomycin in Streptomyces arginensis NRRL 15941. Appl. Environ. Microbiol. 80 (2014) 5021-5027. [PMID: 24907335]
Accepted name: phytol O-acyltransferase
Reaction: an acyl-CoA + phytol = a fatty acid phytyl ester + CoA
Other name(s): phytyl ester synthase; PES1 (gene name); PES2 (gene name); slr2103 (locus name)
Systematic name: acyl-CoA:phytol O-acyltransferase
Comments: The enzyme is found in plant chloroplasts and cyanobacteria. The plant enzyme can also employ acyl carrier proteins and galactolipids as acyl donors, while the enzyme from the cyanobacterium Synechocystis sp. PCC 6803 only uses acyl-CoAs. The enzyme also catalyses the activity of EC 2.3.1.20, diacylglycerol O-acyltransferase.
References:
1. Ischebeck, T., Zbierzak, A.M., Kanwischer, M. and Dormann, P. A salvage pathway for phytol metabolism in Arabidopsis. J. Biol. Chem. 281 (2006) 2470-2477. [PMID: 16306049]
2. Lippold, F., vom Dorp, K., Abraham, M., Holzl, G., Wewer, V., Yilmaz, J.L., Lager, I., Montandon, C., Besagni, C., Kessler, F., Stymne, S. and Dormann, P. Fatty acid phytyl ester synthesis in chloroplasts of Arabidopsis. Plant Cell 24 (2012) 2001-2014. [PMID: 22623494]
3. Aizouq, M., Peisker, H., Gutbrod, K., Melzer, M., Holzl, G. and Dormann, P. Triacylglycerol and phytyl ester synthesis in Synechocystis sp. PCC6803. Proc. Natl. Acad. Sci. USA 117 (2020) 6216-6222. [PMID: 32123083]
4. Tanaka, M., Ishikawa, T., Tamura, S., Saito, Y., Kawai-Yamada, M. and Hihara, Y. Quantitative and qualitative analyses of triacylglycerol production in the wild-type Cyanobacterium Synechocystis sp. PCC 6803 and the strain expressing AtfA from Acinetobacter baylyi ADP1. Plant Cell Physiol. 61 (2020) 1537-1547. [PMID: 32433767]
Accepted name: succinyl-CoA:cyclohexane-1-carboxylate CoA transferase
Reaction: succinyl-CoA + cyclohexane-1-carboxylate = succinate + cyclohexane-1-carbonyl-CoA
Other name(s): Gmet_3304 (locus name)
Systematic name: succinyl-CoA—cyclohexane-1-carboxylate CoA-transferase
Comments: The enzyme, characterized from the bacterium Geobacter metallireducens, participates in an anaerobic degradation pathway for cyclohexane-1-carboxylate. In vitro, the enzyme can use butanoyl-coA as a CoA donor with greater efficiency than succinyl-CoA.
References:
1. Kung, J.W., Meier, A.K., Mergelsberg, M. and Boll, M. Enzymes involved in a novel anaerobic cyclohexane carboxylic acid degradation pathway. J. Bacteriol. 196 (2014) 3667-3674. [PMID: 25112478]
Accepted name: N-hydroxyputrescine acetyltransferase
Reaction: acetyl-CoA + N-hydroxyputrescine = N1-acetyl-N1-hydroxyputrescine + CoA
Glossary: N-hydroxyputrescine = N-hydroxybutane-1,4-diamine
Other name(s): fbsK (gene name)
Systematic name: acetyl-CoA:N-hydroxyputrescine N-acetyltransferase
Comments: The enzyme, characterized from the bacterium Acinetobacter baumannii ATCC 17978, participates in the biosynthesis of fimsbactin siderophores.
References:
1. Proschak, A., Lubuta, P., Grun, P., Lohr, F., Wilharm, G., De Berardinis, V. and Bode, H.B. Structure and biosynthesis of fimsbactins A-F, siderophores from Acinetobacter baumannii and Acinetobacter baylyi. Chembiochem 14 (2013) 633-638. [PMID: 23456955]
2. Yang, J. and Wencewicz, T.A. In vitro reconstitution of fimsbactin biosynthesis from Acinetobacter baumannii. ACS Chem. Biol. 17 (2022) 2923-2935. [PMID: 36122366]
Accepted name: cyclic β-1,2-glucan glucanotransferase
Reaction: Cyclizes part of a (1→2)-β-D-glucan chain by formation of a (1→2)-β-D-glucosidic bond
Systematic name: (1→2)-β-D-glucan:(1→2)-β-D-glucan 2-β-D-[(1→2)-β-D-glucano]-transferase (cyclizing and configuration-retaining)
Comments: This enzyme is the cyclization domain of cyclic β-1,2-glucan synthase. Enzymes from Brucella abortus and Thermoanaerobacter italicus were characterized. The cyclization domain of cyclic β-1,2-glucan synthase is flanked by an N-terminal β-1,2-glucosyltransferase domain (cf. EC 2.4.1.391) and a C-terminal β-1,2-glucoside phosphorylase domain (cf. EC 2.4.1.333), with the former responsible for elongation and the latter for chain length control. The cyclization domain of Thermoanaerobacter italicus cyclizes linear oligosaccharides with a degree of polymerization (DP) of 21 or higher to produce cyclic glucans with DP 17 or higher. The cyclization domain also disproportionates linear β-1,2-glucooligosaccharides without cycling. The entire cyclic β-1,2-glucan synthase from Brucella abortus synthesizes cyclic β-1,2-glucans with DP 17-22.
References:
1. Inon de Iannino, N., Briones, G., Tolmasky, M. and Ugalde, R.A. Molecular cloning and characterization of cgs, the Brucella abortus cyclic β(1-2) glucan synthetase gene: genetic complementation of Rhizobium meliloti ndvB and Agrobacterium tumefaciens chvB mutants. J. Bacteriol. 180 (1998) 4392-4400. [PMID: 9721274]
2. Guidolin, L.S., Ciocchini, A.E., Inon de Iannino, N. and Ugalde, R.A. Functional mapping of Brucella abortus cyclic β-1,2-glucan synthase: identification of the protein domain required for cyclization. J. Bacteriol. 191 (2009) 1230-1238. [PMID: 19074375]
3. Guidolin, L.S., Morrone Seijo, S.M., Guaimas, F.F., Comerci, D.J. and Ciocchini, A.E. Interaction network and localization of Brucella abortus membrane proteins involved in the synthesis, transport, and succinylation of cyclic β-1,2-glucans. J. Bacteriol. 197 (2015) 1640-1648. [PMID: 25733613]
4. Tanaka, N., Saito, R., Kobayashi, K., Nakai, H., Kamo, S., Kuramochi, K., Taguchi, H., Nakajima, M. and Masaike, T. Functional and structural analysis of a cyclization domain in a cyclic β-1,2-glucan synthase. Appl. Microbiol. Biotechnol. 108 (2024) 187. [PMID: 38300345]
Accepted name: hexaprenyl diphosphate synthase (prenyl-diphosphate specific)
Reaction: prenyl diphosphate + 5 3-methylbut-3-en-1-yl diphosphate = all-trans-hexaprenyl diphosphate + 5 diphosphate
Glossary: prenyl diphosphate = dimethylallyl diphosphate
3-methylbut-3-en-1-yl diphosphate = isopentenyl diphosphate
Other name(s): HexPPS
Systematic name: prenyl-diphosphate:3-methylbut-3-en-1-yl-diphosphate transferase (adding 5 units of 3-methylbut-3-en-1-yl)
Comments: This activity has been characterized from a number of fungal bifunctional enzymes. Following the formation of hexaprenyl diphosphate, a different domain in the enzymes catalyses its cyclization into a triterpene (see EC 4.2.3.221, macrophomene synthase and EC 4.2.3.220, talaropentaene synthase). cf. EC 2.5.1.82, hexaprenyl diphosphate synthase [geranylgeranyl-diphosphate specific].
References:
1. Tao, H., Lauterbach, L., Bian, G., Chen, R., Hou, A., Mori, T., Cheng, S., Hu, B., Lu, L., Mu, X., Li, M., Adachi, N., Kawasaki, M., Moriya, T., Senda, T., Wang, X., Deng, Z., Abe, I., Dickschat, J.S. and Liu, T. Discovery of non-squalene triterpenes. Nature 606 (2022) 414-419. [PMID: 35650436]
Accepted name: hapalindole G dimethylallyltransferase
Reaction: (1) prenyl diphosphate + hapalindole G = ambiguine A + diphosphate
(2) prenyl diphosphate + hapalindole U = ambiguine H + diphosphate
For diagram of reaction click here
Glossary: prenyl diphosphate = dimethylallyl diphosphate
hapalindole G = (6aS,8R,9R,10R,10aS)-8-chloro-10-isocyano-6,6,9-trimethyl-9-vinyl-2,6,6a,7,8,9,10,10a-octahydronaphtho[1,2,3-cd]indole
ambiguine A = (6aS,8R,9R,10R,10aS)-8-chloro-10-isocyano-6,6,9-trimethyl-1-(2-methylbut-3-en-2-yl)-9-vinyl-2,6,6a,7,8,9,10,10a-octahydronaphtho[1,2,3-cd]indole
hapalindole U = (6aS,9R,10R,10aS)-10-isocyano-6,6,9-trimethyl-9-vinyl-2,6,6a,7,8,9,10,10a-octahydronaphtho[1,2,3-cd]indole
ambiguine H = (6aS,9R,10R,10aS)-9-ethenyl-10-isocyano-6,6,9-trimethyl-1-(2-methylbut-3-en-2-yl)-2,6,6a,7,8,9,10,10a-octahydronaphtho[1,2,3-cd]indole
Other name(s): ambP3 (gene name); famD1 (gene name)
Systematic name: prenyl-diphosphate:hapalindole G prenyltransferase (ambiguine A-forming)
Comments: Requires Mg2+. The enzyme, characterized from the cyanobacterium Fischerella ambigua UTEX 1903, is involved in the biosynthesis of hapalindole-type alkaloids. When acting on hapalindole U, the enzyme forms ambiguine H.
References:
1. Hillwig, M.L., Zhu, Q. and Liu, X. Biosynthesis of ambiguine indole alkaloids in cyanobacterium Fischerella ambigua. ACS Chem. Biol. 9 (2014) 372-377. [PMID: 24180436]
Accepted name: L-arginine:2-oxoglutarate transaminase
Reaction: L-arginine + 2-oxoglutarate = 5-guanidino-2-oxopentanoate + L-glutamate
Other name(s): argM (gene name); arginine-α-ketoglutarate transaminase
Systematic name: L-arginine:2-oxoglutarate aminotransferase
Comments: Requires pyridoxal 5'-phosphate. The enzyme, characterized from several bacterial species, is known to participate in L-arginine degradation and in the biosynthesis of the rare amino acid (3R)-3-methyl-L-arginine. The enzyme from Streptomyces arginensis also catalyses the activity of EC 2.6.1.126, L-aspartate:5-guanidino-3-methyl-2-oxopentanoate transaminase.
References:
1. Tachiki, T., Kohno, H., Sugiyama, K., Matsubara, T. and Tochikura, T. Purification, properties and formation of arginine-α-ketoglutarate transaminase in Arthrobacter simplex. Biochim. Biophys Acta 615 (1980) 79-84. [PMID: 7426667]
2. Feng, J., Wu, J., Gao, J., Xia, Z., Deng, Z. and He, X. Biosynthesis of the β-methylarginine residue of peptidyl nucleoside arginomycin in Streptomyces arginensis NRRL 15941. Appl. Environ. Microbiol. 80 (2014) 5021-5027. [PMID: 24907335]
Accepted name: L-aspartate:5-guanidino-3-methyl-2-oxopentanoate transaminase
Reaction: L-aspartate + (3R)-5-guanidino-3-methyl-2-oxopentanoate = oxaloacetate + (3R)-3-methyl-L-arginine
Other name(s): argM (gene name); mrsB (gene name)
Systematic name: L-aspartate:5-guanidino-3-methyl-2-oxopentanoate aminotransferase
Comments: Requires pyridoxal 5'-phosphate. The enzyme, characterized from several bacterial species, participates in the biosynthesis of the rare amino acid (3R)-3-methyl-L-arginine. The enzyme from Streptomyces arginensis also catalyses the activity of EC 2.6.1.125, L-arginine:2-oxoglutarate transaminase.
References:
1. Braun, S.D., Hofmann, J., Wensing, A., Ullrich, M.S., Weingart, H., Völksch, B. and Spiteller, D. Identification of the biosynthetic gene cluster for 3-methylarginine, a toxin produced by Pseudomonas syringae pv. syringae 22d/93. Appl. Environ. Microbiol. 76 (2010) 2500-2508. [PMID: 20190091]
2. Feng, J., Wu, J., Gao, J., Xia, Z., Deng, Z. and He, X. Biosynthesis of the β-methylarginine residue of peptidyl nucleoside arginomycin in Streptomyces arginensis NRRL 15941. Appl. Environ. Microbiol. 80 (2014) 5021-5027. [PMID: 24907335]
Accepted name: MASTL-subfamily protein kinase
Reaction: (1) ATP + [endosulfine family protein]-L-serine = ADP + [endosulfine family protein]-O-phospho-L-serine
(2) ATP + [endosulfine family protein]-L-threonine = ADP + [endosulfine family protein]-O-phospho-L-threonine
Glossary: MASTL = microtubule-associated
Other name(s): MASTL; gwl; greatwall kinase; RIM15; microtubule-associated (MASTL)-subfamily-protein kinase.
Systematic name: ATP:[endosulfine family protein] phosphotransferase (Ser/Thr-phosphorylating)
Comments: Requires Mg2+. Peptide array data suggest that MASTL prefers to phosphorylate Ser over Thr, followed at position +1 by a bulky hydrophobic (Met, Leu, Phe or Tyr) and with an aromatic residue in the -2 position [4]. Its main role in animal systems is in the regulation of mitosis by phosphorylating a conserved site on endosulfine family proteins (ENSA and ARPP-19 in human), causing them to inhibit the protein phosphatase 2A-B55 [protein phosphatase 2A (PP2A) holoenzyme complex containing a B55-family regulatory subunit] [2].
References:
1. Pearce, L.R., Komander, D. and Alessi, D.R. The nuts and bolts of AGC protein kinases. Nat. Rev. Mol. Cell. Biol. 11 (2010) 9-22. [PMID: 20027184]
2. Castro, A. and Lorca, T. Greatwall kinase at a glance. J. Cell Sci. 131 (2018) . [PMID: 30355803]
3. Goguet-Rubio, P., Amin, P., Awal, S., Vigneron, S., Charrasse, S., Mechali, F., Labbe, J.C., Lorca, T. and Castro, A. PP2A-B55 holoenzyme regulation and cancer. Biomolecules 10 (2020) . [PMID: 33266510]
4. Johnson, J.L., Yaron, T.M., Huntsman, E.M., Kerelsky, A., Song, J., Regev, A., Lin, T.Y., Liberatore, K., Cizin, D.M., Cohen, B.M., Vasan, N., Ma, Y., Krismer, K., Robles, J.T., van de Kooij, B., van Vlimmeren, A.E., Andree-Busch, N., Kaufer, N.F., Dorovkov, M.V., Ryazanov, A.G., Takagi, Y., Kastenhuber, E.R., Goncalves, M.D., Hopkins, B.D., Elemento, O., Taatjes, D.J., Maucuer, A., Yamashita, A., Degterev, A., Uduman, M., Lu, J., Landry, S.D., Zhang, B., Cossentino, I., Linding, R., Blenis, J., Hornbeck, P.V., Turk, B.E., Yaffe, M.B. and Cantley, L.C. An atlas of substrate specificities for the human serine/threonine kinome. Nature 613 (2023) 759-766. [PMID: 36631611]
Accepted name: MAST-subfamily protein kinase
Reaction: (1) ATP + [protein]-L-serine = ADP + [protein]-O-phospho-L-serine
(2) ATP + [protein]-L-threonine = ADP + [protein]-O-phospho-L-threonine
Other name(s): microtubule-associated serine/threonine-protein kinase; MAST1; MAST2; MAST3; MAST4; MAST205; SAST; IREH1; dop; kin-4
Comments: Requires Mg2+. MAST (Microtubule Associated Serine/Threonine) kinases are eukaryotic-wide kinases with roles in microtubule function, PTEN regulation and a variety of neuronal functions. They are found in most eukaryotes, though lost from most fungi and ciliates. MAST kinases associate with their substrates via their PDZ domains. Substrates include the PTEN phosphatase (EC 3.1.3.67) in human and nematodes, and Dlic (Dynein light intermediate chain) in Drosophila. The latter is phosphorylated on Ser401.
References:
1. Valiente, M., Andres-Pons, A., Gomar, B., Torres, J., Gil, A., Tapparel, C., Antonarakis, S.E. and Pulido, R. Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine/threonine kinases. J. Biol. Chem. 280 (2005) 28936-28943. [PMID: 15951562]
2. An, S.WA., Choi, E.S., Hwang, W., Son, H.G., Yang, J.S., Seo, K., Nam, H.J., Nguyen, N.TH., Kim, E.JE., Suh, B.K., Kim, Y., Nakano, S., Ryu, Y., Man Ha, C., Mori, I., Park, S.K., Yoo, J.Y., Kim, S. and Lee, S.V. KIN-4/MAST kinase promotes PTEN-mediated longevity of Caenorhabditis elegans via binding through a PDZ domain. Aging Cell 18 (2019) e12906. [PMID: 30773781]
Accepted name: betainyl-CoA thioesterase
Reaction: betaine-CoA + H2O = glycine betaine + CoA
Glossary: betaine-CoA = glycinebetainyl-CoA = betainyl-CoA = N,N,N-trimethylglycyl-CoA
Other name(s): cdhB (gene name)
Systematic name: betaine-CoA hydrolase
Comments: The enzyme, characterized from the bacterium Pseudomonas aeruginosa, is involved in an L-carnitine degradation pathway.
References:
1. Wargo, M.J. and Hogan, D.A. Identification of genes required for Pseudomonas aeruginosa carnitine catabolism. Microbiology (Reading) 155 (2009) 2411-2419. [PMID: 19406895]
2. Bastard, K., Smith, A.A., Vergne-Vaxelaire, C., Perret, A., Zaparucha, A., De Melo-Minardi, R., Mariage, A., Boutard, M., Debard, A., Lechaplais, C., Pelle, C., Pellouin, V., Perchat, N., Petit, J.L., Kreimeyer, A., Medigue, C., Weissenbach, J., Artiguenave, F., De Berardinis, V., Vallenet, D. and Salanoubat, M. Revealing the hidden functional diversity of an enzyme family. Nat. Chem. Biol. 10 (2014) 42-49. [PMID: 24240508]
Accepted name: 4'-phosphopantetheine phosphatase
Reaction: 4'-phosphopantetheine + H2O = pantetheine + phosphate
Glossary: pantetheine = (2R)-2,4-dihydroxy-3,3-dimethyl-N-{3-oxo-3-[(2-sulfanylethyl)amino]propyl}butanamide
Other name(s): thnH (gene name); PANK4 (gene name)
Systematic name: 4'-phosphopantetheine phosphohydrolase
Comments: The enzyme has been characterized from mammals and from the bacterium Streptantibioticus cattleyicolor. In mammals it hydrolyses excess 4'-phosphopantetheine to prevent cell damage. In S. cattleyicolor it participates in the biosynthesis of the β-lactam antibiotic thienamycin.
References:
1. Freeman, M.F., Moshos, K.A., Bodner, M.J., Li, R. and Townsend, C.A. Four enzymes define the incorporation of coenzyme A in thienamycin biosynthesis. Proc. Natl. Acad. Sci. USA 105 (2008) 11128-11133. [PMID: 18678912]
2. Huang, L., Khusnutdinova, A., Nocek, B., Brown, G., Xu, X., Cui, H., Petit, P., Flick, R., Zallot, R., Balmant, K., Ziemak, M.J., Shanklin, J., de Crecy-Lagard, V., Fiehn, O., Gregory, J.F., 3rd, Joachimiak, A., Savchenko, A., Yakunin, A.F. and Hanson, A.D. A family of metal-dependent phosphatases implicated in metabolite damage-control. Nat. Chem. Biol. 12 (2016) 621-627. [PMID: 27322068]
Accepted name: D-arabinan exo β-(1,2)-arabinofuranosidase (non-reducing end)
Reaction: Hydrolysis of terminal non-reducing β-D-arabinofuranoside residues in D-arabinans
Other name(s): exo-β-D-arabinofuranosidase; ExoMA2
Systematic name: β-D-arabinofuranoside non-reducing end β-D-arabinofuranosidase (configuration-retaining)
Comments: The enzyme, characterized from the bacterium Microbacterium arabinogalactanolyticum, hydrolyses β-D-arabinofuranosides from the non-reducing terminal of D-arabinan core structure of lipoarabinomannan and arabinogalactan of mycobacterial cell wall. cf. EC 3.2.1.55, non-reducing end α-L-arabinofuranosidase; EC 3.2.1.185, non-reducing end β-L-arabinofuranosidase; EC 3.2.1.225, D-arabinan exo α-(1,3)/(1,5)-arabinofuranosidase (non-reducing end); and EC 3.2.1.226, D-arabinan endo α-(1,5)-arabinofuranosidase.
References:
1. Shimokawa, M., Ishiwata, A., Kashima, T., Nakashima, C., Li, J., Fukushima, R., Sawai, N., Nakamori, M., Tanaka, Y., Kudo, A., Morikami, S., Iwanaga, N., Akai, G., Shimizu, N., Arakawa, T., Yamada, C., Kitahara, K., Tanaka, K., Ito, Y., Fushinobu, S. and Fujita, K. Identification and characterization of endo-α-, exo-α-, and exo-β-D-arabinofuranosidases degrading lipoarabinomannan and arabinogalactan of mycobacteria. Nat. Commun. 14 (2023) 5803. [PMID: 37726269]
Accepted name: D-arabinan exo α-(1,3)/(1,5)-arabinofuranosidase (non-reducing end)
Reaction: Hydrolysis of terminal non-reducing α-D-arabinofuranoside residues in D-arabinans
Other name(s): exo-α-D-arabinofuranosidase; DgGH172a; DgGH172b; DgGH172c; NocGH172; MycGH172; ExoMA1
Systematic name: α-D-arabinofuranoside non-reducing end α-D-arabinofuranosidase (configuration-retaining)
Comments: The enzyme hydrolyses α-D-arabinofuranosides with (1,3)- and (1,5)-linkages in D-arabinan core structure of lipoarabinomannan and arabinogalactan of mycobacterial cell wall. cf. EC 3.2.1.55, non-reducing end α-L-arabinofuranosidase; cf. EC 3.2.1.224, D-arabinan exo β-(1,2)-arabinofuranosidase (non-reducing end); cf. EC 3.2.1.226, D-arabinan endo α-(1,5)-arabinofuranosidase.
References:
1. Al-Jourani, O., Benedict, S.T., Ross, J., Layton, A.J., van der Peet, P., Marando, V.M., Bailey, N.P., Heunis, T., Manion, J., Mensitieri, F., Franklin, A., Abellon-Ruiz, J., Oram, S.L., Parsons, L., Cartmell, A., Wright, G.SA., Basle, A., Trost, M., Henrissat, B., Munoz-Munoz, J., Hirt, R.P., Kiessling, L.L., Lovering, A.L., Williams, S.J., Lowe, E.C. and Moynihan, P.J. Identification of D-arabinan-degrading enzymes in mycobacteria. Nat. Commun. 14 (2023) 2233. [PMID: 37076525]
2. Shimokawa, M., Ishiwata, A., Kashima, T., Nakashima, C., Li, J., Fukushima, R., Sawai, N., Nakamori, M., Tanaka, Y., Kudo, A., Morikami, S., Iwanaga, N., Akai, G., Shimizu, N., Arakawa, T., Yamada, C., Kitahara, K., Tanaka, K., Ito, Y., Fushinobu, S. and Fujita, K. Identification and characterization of endo-α-, exo-α-, and exo-β-D-arabinofuranosidases degrading lipoarabinomannan and arabinogalactan of mycobacteria. Nat. Commun. 14 (2023) 5803. [PMID: 37726269]
Accepted name: D-arabinan endo α-(1,5)-arabinofuranosidase
Reaction: Hydrolysis of internal α-D-arabinofuranoside bonds in D-arabinans
Other name(s): endo-D-arabinanase (ambiguous); DgGH4185a; DgGH4185b; MyxoGH4185; PhageGH4185; Mab4185; EndoMA1; EndoMA2.
Systematic name: D-arabinan endo α-(1,5)-arabinofuranosidase (configuration-retaining)
Comments: The enzyme hydrolyses α-(1,5)-D-arabinofuranoside bonds in D-arabinan core structure of lipoarabinomannan and arabinogalactan of mycobacterial cell wall. cf. EC 3.2.1.224, D-arabinan exo β-(1,2)-arabinofuranosidase (non-reducing end); cf. EC 3.2.1.225, D-arabinan exo α-(1,3)/(1,5)-arabinofuranosidase (non-reducing end).
References:
1. Kotani, S., Kato, T., Matsuda, T., Kato, K. and Misaki, A. Chemical structure of the antigenic determinants of cell wall polysaccharide of Mycobacterium tuberculosis strain H37Rv. Biken J 14 (1971) 379-387. [PMID: 4113500]
2. Al-Jourani, O., Benedict, S.T., Ross, J., Layton, A.J., van der Peet, P., Marando, V.M., Bailey, N.P., Heunis, T., Manion, J., Mensitieri, F., Franklin, A., Abellon-Ruiz, J., Oram, S.L., Parsons, L., Cartmell, A., Wright, G.SA., Basle, A., Trost, M., Henrissat, B., Munoz-Munoz, J., Hirt, R.P., Kiessling, L.L., Lovering, A.L., Williams, S.J., Lowe, E.C. and Moynihan, P.J. Identification of D-arabinan-degrading enzymes in mycobacteria. Nat. Commun. 14 (2023) 2233. [PMID: 37076525]
3. Shimokawa, M., Ishiwata, A., Kashima, T., Nakashima, C., Li, J., Fukushima, R., Sawai, N., Nakamori, M., Tanaka, Y., Kudo, A., Morikami, S., Iwanaga, N., Akai, G., Shimizu, N., Arakawa, T., Yamada, C., Kitahara, K., Tanaka, K., Ito, Y., Fushinobu, S. and Fujita, K. Identification and characterization of endo-α-, exo-α-, and exo-β-D-arabinofuranosidases degrading lipoarabinomannan and arabinogalactan of mycobacteria. Nat. Commun. 14 (2023) 5803. [PMID: 37726269]
Accepted name: arginine dihydrolase
Reaction: L-arginine + 2 H2O = L-ornithine + CO2 + 2 ammonia
Other name(s): argZ (gene name)
Systematic name: L-arginine aminodihydrolase (L-ornithine-forming)
Comments: The enzyme, characterized from different cyanobacterial species, is highly specific to arginine and does not require a metal cofactor. The enzyme from Nostoc is bifunctional, and also catalyses the activity of EC 4.3.1.12, ornithine cyclodeaminase.
References:
1. Zhang, H., Liu, Y., Nie, X., Liu, L., Hua, Q., Zhao, G.P. and Yang, C. The cyanobacterial ornithine-ammonia cycle involves an arginine dihydrolase. Nat. Chem. Biol. 14 (2018) 575-581. [PMID: 29632414]
2. Burnat, M., Picossi, S., Valladares, A., Herrero, A. and Flores, E. Catabolic pathway of arginine in Anabaena involves a novel bifunctional enzyme that produces proline from arginine. Mol. Microbiol. 111 (2019) 883-897. [PMID: 30636068]
3. Zhuang, N., Zhang, H., Li, L., Wu, X., Yang, C. and Zhang, Y. Crystal structures and biochemical analyses of the bacterial arginine dihydrolase ArgZ suggests a "bond rotation" catalytic mechanism. J. Biol. Chem. 295 (2020) 2113-2124. [PMID: 31914412]
Accepted name: salsolinol synthase
Reaction: (R)-salsolinol + H2O = dopamine + acetaldehyde
For diagram of reaction click here
Glossary: (R)-salsolinol = (+)-salsolinol = (1R)-1,2,3,4-tetrahydro-1-methylisoquinoline-6,7-diol
Other name(s): Sal synthase
Systematic name: (R)-salsolinol dopamine-hydrolase (acetaldehyde-forming)
Comments: The enzyme, present in mammalian brains, forms the catechol isoquinoline (R)-salsolinol. This compound can be metabolized to (R)-N-methylsalsolinol, a 1-methyl-4-phenylpyridinium-like neurotoxin that impairs the function of dopaminergic neurons, causing the clinical symptoms of Parkinson's disease.
References:
1. Naoi, M., Maruyama, W., Dostert, P., Kohda, K. and Kaiya, T. A novel enzyme enantio-selectively synthesizes (R)-salsolinol, a precursor of a dopaminergic neurotoxin, N-methyl-(R)-salsolinol. Neurosci. Lett. 212 (1996) 183-186. [PMID: 8843103]
2. Naoi, M., Maruyama, W., Takahashi, T., Akao, Y. and Nakagawa, Y. Involvement of endogenous N-methyl-(R)-salsolinol in Parkinson's disease: induction of apoptosis and protection by (–)deprenyl. J Neural Transm Suppl (2000) 111-121. [PMID: 11128601]
3. Chen, X., Zheng, X., Ali, S., Guo, M., Zhong, R., Chen, Z., Zhang, Y., Qing, H. and Deng, Y. Isolation and sequencing of salsolinol synthase, an enzyme catalyzing salsolinol biosynthesis. ACS Chem Neurosci 9 (2018) 1388-1398. [PMID: 29602279]
4. Xiong, Q., Zheng, X., Wang, J., Chen, Z., Deng, Y., Zhong, R., Wang, J. and Chen, X. Sal synthase induced cytotoxicity of PC12 cells through production of the dopamine metabolites salsolinol and N-methyl-salsolinol. J Integr Neurosci 21 (2022) 71. [PMID: 35364659]
Accepted name: strictosidine synthase
Reaction: 3-α(S)-strictosidine + H2O = tryptamine + secologanin
For diagram of reaction click here
Other name(s): strictosidine synthetase; STR; 3-α(S)-strictosidine tryptamine-lyase; 3-α(S)-strictosidine tryptamine-lyase (secologanin-forming)
Systematic name: 3-α(S)-strictosidine tryptamine-hydrolase (secologanin-forming)
Comments: Catalyses a Pictet-Spengler reaction between the aldehyde group of secologanin and the amino group of tryptamine [4,5]. Involved in the biosynthesis of the monoterpenoid indole alkaloids.
References:
1. Treimer, J.K. and Zenk, M.H. Purification and properties of strictosidine synthase, the key enzyme in indole alkaloid formation. Eur. J. Biochem. 101 (1979) 225-233. [PMID: 510306]
2. Kutchan, T.M. Strictosidine: from alkaloid to enzyme to gene. Phytochemistry 32 (1993) 493-506. [PMID: 7763429]
3. de Waal, A., Meijer, A.H. and Verpoorte, R. Strictosidine synthase from Catharanthus roseus: purification and characterization of multiple forms. Biochem. J. 306 (1995) 571-580. [PMID: 7887913]
4. Ruppert, M., Woll, J., Giritch, A., Genady, E., Ma, X. and Stöckigt, J. Functional expression of an ajmaline pathway-specific esterase from Rauvolfia in a novel plant-virus expression system. Planta 222 (2005) 888-898. [PMID: 16133216]
5. McCoy, E., Galan, M.C. and O'Connor, S.E. Substrate specificity of strictosidine synthase. Bioorg. Med. Chem. Lett. 16 (2006) 2475-2478. [PMID: 16481164]
6. Ma, X., Panjikar, S., Koepke, J., Loris, E. and Stöckigt, J. The structure of Rauvolfia serpentina strictosidine synthase is a novel six-bladed β-propeller fold in plant proteins. Plant Cell 18 (2006) 907-920. [PMID: 16531499]
Accepted name: (S)-norcoclaurine synthase
Reaction: (S)-norcoclaurine + H2O = dopamine + 4-hydroxyphenylacetaldehyde
For diagram of reaction, click here
Glossary: dopamine = 4-(2-aminoethyl)benzene-1,2-diol
Other name(s): (S)-norlaudanosoline synthase; 4-hydroxyphenylacetaldehyde hydro-lyase (adding dopamine); 4-hydroxyphenylacetaldehyde hydro-lyase [adding dopamine; (S)-norcoclaurine-forming]
Systematic name: (S)-norcoclaurine dopamine hydrolase (4-hydroxyphenylacetaldehyde-forming)
Comments: The reaction makes a six-membered ring by forming a bond between C-6 of the 3,4-dihydroxyphenyl group of the dopamine and C-1 of the aldehyde in the imine formed between the substrates. The product is the precursor of the benzylisoquinoline alkaloids in plants. The enzyme, formerly known as (S)-norlaudanosoline synthase, will also catalyse the reaction of 4-(2-aminoethyl)benzene-1,2-diol + (3,4-dihydroxyphenyl)acetaldehyde to form (S)-norlaudanosoline, but this alkaloid has not been found to occur in plants.
References:
1. Stadler, R., Zenk, M.H. A revision of the generally accepted pathway for the biosynthesis of the benzyltetrahydroisoquinoline reticuline. Liebigs Ann. Chem. (1990) 555-562.
2. Stadler, R., Kutchan, T.M., Zenk, M.H. (S)-Norcoclaurine is the central intermediate in benzylisoquinoline alkaloid biosynthesis. Phytochemistry 28 (1989) 1083-1086.
3. Samanani, N. and Facchini, P.J. Purification and characterization of norcoclaurine synthase. The first committed enzyme in benzylisoquinoline alkaloid biosynthesis in plants. J. Biol. Chem. 277 (2002) 33878-33883. [PMID: 12107162]
Accepted name: deacetylisoipecoside synthase
Reaction: deacetylisoipecoside + H2O = dopamine + secologanin
For diagram of reaction, click here
Glossary: dopamine = 4-(2-aminoethyl)benzene-1,2-diol
Other name(s): deacetylisoipecoside dopamine-lyase; deacetylisoipecoside dopamine-lyase (secologanin-forming)
Systematic name: deacetylisoipecoside dopamine-hydolase (secologanin-forming)
Comments: The enzyme from the leaves of Alangium lamarckii differs in enantiomeric specificity from EC 3.5.99.16, deacetylipecoside synthase. The product is rapidly converted to demethylisoalangiside.
References:
1. DeEknamkul, W., Ounaroon, A., Tanahashi, T., Kutchan, T. and Zenk, M.H. Enzymatic condensation of dopamine and secologanin by cell-free extracts of Alangium lamarckii. Phytochemistry 45 (1997) 477-484.
Accepted name: deacetylipecoside synthase
Reaction: deacetylipecoside + H2O = dopamine + secologanin
For diagram of reaction click here
Glossary: dopamine = 4-(2-aminoethyl)benzene-1,2-diol
Other name(s): deacetylipecoside dopamine-lyase; deacetylipecoside dopamine-lyase (secologanin-forming)
Systematic name: deacetylipecoside dopamine-hydroyase (secologanin-forming)
Comments: The enzyme from the leaves of Alangium lamarckii differs in enantiomeric specificity from EC 3.5.99.15, deacetylisoipecoside synthase. The product is rapidly converted to demethylalangiside.
References:
1. DeEknamkul, W., Ounaroon, A., Tanahashi, T., Kutchan, T. and Zenk, M.H. Enzymatic condensation of dopamine and secologanin by cell-free extracts of Alangium lamarckii. Phytochemistry 45 (1997) 477-484.
2. De-Eknamkul, W., Suttipanta, N. and Kutchan, T.M. Purification and characterization of deacetylipecoside synthase from Alangium lamarckii Thw. Phytochemistry 55 (2000) 177-181. [PMID: 11065292]
Accepted name: coenzyme A diphosphatase
Reaction: coenzyme A + H2O = adenosine 3',5'-bisphosphate + 4'-phosphopantetheine
Other name(s): CoA pyrophosphatase; coenzyme A pyrophosphatase; CoA diphosphohydrolase; Nudt19; Nudt7; thnR (gene name)
Systematic name: coenzyme A 4'-phosphopantetheine phosphohydrolase
Comments: The enzyme belongs to the Nudix hydrolase family. It has been reported from bacteria, yeast, and mammals. Activity is higher with oxidized disulfide CoA than with reduced CoA.
References:
1. Xu, W., Shen, J., Dunn, C.A., Desai, S. and Bessman, M.J. The Nudix hydrolases of Deinococcus radiodurans. Mol. Microbiol. 39 (2001) 286-290. [PMID: 11136450]
2. Gasmi, L. and McLennan, A.G. The mouse Nudt7 gene encodes a peroxisomal nudix hydrolase specific for coenzyme A and its derivatives. Biochem. J. 357 (2001) 33-38. [PMID: 11415433]
3. Kang, L.W., Gabelli, S.B., Bianchet, M.A., Xu, W.L., Bessman, M.J. and Amzel, L.M. Structure of a coenzyme A pyrophosphatase from Deinococcus radiodurans: a member of the Nudix family. J. Bacteriol. 185 (2003) 4110-4118. [PMID: 12837785]
4. Freeman, M.F., Moshos, K.A., Bodner, M.J., Li, R. and Townsend, C.A. Four enzymes define the incorporation of coenzyme A in thienamycin biosynthesis. Proc. Natl. Acad. Sci. USA 105 (2008) 11128-11133. [PMID: 18678912]
5. Shumar, S.A., Kerr, E.W., Geldenhuys, W.J., Montgomery, G.E., Fagone, P., Thirawatananond, P., Saavedra, H., Gabelli, S.B. and Leonardi, R. Nudt19 is a renal CoA diphosphohydrolase with biochemical and regulatory properties that are distinct from the hepatic Nudt7 isoform. J. Biol. Chem. 293 (2018) 4134-4148. [PMID: 29378847]
[EC 3.6.4.13 Transferred entry: RNA helicase. Now covered by EC 5.6.2.5, RNA 5'-3' helicase, EC 5.6.2.6, RNA 3'-5' helicase and EC 5.6.2.7, DEAD-box RNA helicase (EC 3.6.4.13 created 2009, deleted 2024]
Accepted name: carboxyaminopropylagmatine decarboxylase
Reaction: N1-[(S)-3-amino-3-carboxypropyl]agmatine = N1-(3-aminopropyl)agmatine + CO2
Glossary: N1-[(S)-3-amino-3-carboxypropyl]agmatine = carboxyaminopropylagmatine
N1-(3-aminopropyl)agmatine = aminopropylagmatine
Other name(s): sll0873 (locus name)
Systematic name: N1-[(S)-3-amino-3-carboxypropyl]agmatine carboxy-lyase
Comments: A pyridoxal-phosphate protein. The enzyme, characterized from the cyanobacterium Synechocystis sp. PCC 6803, participates in a biosynthetic pathway for spermidine.
References:
1. Xi, H., Nie, X., Gao, F., Liang, X., Li, H., Zhou, H., Cai, Y. and Yang, C. A bacterial spermidine biosynthetic pathway via carboxyaminopropylagmatine. Sci Adv 9 (2023) eadj9075. [PMID: 37878710]
Accepted name: ferulate hydratase/lyase
Reaction: ferulate + H2O = vanillin + acetate (overall reaction)
(1a) ferulate + H2O = 3-hydroxy-3-(4-hydroxy-3-methoxyphenyl)propanoate
(1b) 3-hydroxy-3-(4-hydroxy-3-methoxyphenyl)propanoate = vanillin + acetate
For diagram of reaction click here
Glossary: ferulate = 4-hydroxy-3-methoxycinnamate
vanillin = 4-hydroxy-3-methoxybenzaldehyde
Other name(s): vanillin synthase; VpVan; VAN; ferulate aldolase
Systematic name: ferulate acetate-lyase (vanillin-forming)
Comments: The enzyme is located in the chloroplasts of vanilla pods of the orchid Vanilla planifolia. It also converts ferulic acid 4-O-β-D-glucopyranoside to vanillin 4-O-β-D-glucopyranoside.
References:
1. Gallage, N.J., Hansen, E.H., Kannangara, R., Olsen, C.E., Motawia, M.S., Jørgensen, K., Holme, I., Hebelstrup, K., Grisoni, M. and Møller, B.L. Vanillin formation from ferulic acid in Vanilla planifolia is catalysed by a single enzyme. Nat. Commun. 5 (2014) 4037. [PMID: 24941968]
2. Kundu, A. Vanillin biosynthetic pathways in plants. Planta 245 (2017) 1069-1078. [PMID: 28357540]
3. Gallage, N.J., Jørgensen, K., Janfelt, C., Nielsen, A.JZ., Naake, T., Dunski, E., Dalsten, L., Grisoni, M. and Møller, B.L. The intracellular localization of the vanillin biosynthetic machinery in pods of Vanilla planifolia. Plant Cell Physiol. 59 (2018) 304-318. [PMID: 29186560]
Accepted name: 4-coumarate hydratase/lyase
Reaction: 4-coumarate + H2O = 4-hydroxybenzaldehyde + acetate (overall reaction)
(1a) 4-coumarate + H2O = 3-hydroxy-3-(4-hydroxyphenyl)propanoate
(1b) 3-hydroxy-3-(4-hydroxyphenyl)propanoate = 4-hydroxybenzaldehyde + acetate
Glossary: 4-coumarate = (2E)-3-(4-hydroxyphenyl)acrylate = (2E)-3-(4-hydroxyphenyl)prop-2-enoate
Other name(s): 4-hydroxybenzaldehyde synthase; 4HBS
Systematic name: 4-coumarate acetate-lyase (4-hydroxybenzaldehyde-forming)
Comments: The enzyme has been purified from vanilla pods of the orchid Vanilla planifolia. It is highly specific for 4-coumarate. Similar compounds such as cinnamate, caffeate, sinapate and o-coumarate are not substrates.
References:
1. Podstolski, A., Havkin-Frenkel, D., Malinowski, J., Blount, J.W., Kourteva, G. and Dixon, R.A. Unusual 4-hydroxybenzaldehyde synthase activity from tissue cultures of the vanilla orchid Vanilla planifolia. Phytochemistry 61 (2002) 611-620. [PMID: 12423881]
Accepted name: 5,8-dihydroxy-2-naphthoate synthase
Reaction: cyclic dehypoxanthine futalosine = 5,8-dihydroxy-2-naphthoate + dihydroxyacetone
For diagram of reaction click here
Glossary: cyclic dehypoxanthine futalosine = (1R,3'S,4'R)-3',4',5'-trihydroxy-4-oxo-2,3-dihydrospiro[naphthalene-1,2'-oxolane]-6-carboxylate
5,8-dihydroxy-2-naphthoate = 5,8-dihydroxynaphthalene-2-carboxylate
Other name(s): mqnD (gene name); 1,4-dihydroxy-6-naphthoate synthase (incorrect)
Systematic name: cyclic dehypoxanthine futalosine lyase (dihydroxyacetone-forming)
Comments: The enzyme participates in alternative menaquinone biosynthesis pathways known as the futalosine and modified futalosine pathways, which occurs in some bacterial species including several human pathogens such as Helicobacter pylori, Campylobacter jejuni, and Chlamydia.
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. Arai, R., Murayama, K., Uchikubo-Kamo, T., Nishimoto, M., Toyama, M., Kuramitsu, S., Terada, T., Shirouzu, M. and Yokoyama, S. Crystal structure of MqnD (TTHA1568), a menaquinone biosynthetic enzyme from Thermus thermophilus HB8. J. Struct. Biol. 168 (2009) 575-581. [PMID: 19602440]
3. Manion-Sommerhalter, H.R., Fedoseyenko, D., Joshi, S. and Begley, T.P. Menaquinone biosynthesis: the mechanism of 5,8-dihydroxy-2-naphthoate synthase (MqnD). Biochemistry 60 (2021) 1947-1951. [PMID: 34143602]
[EC 4.2.1.78 Transferred entry: (S)-norcoclaurine synthase. Now EC 3.5.99.14, (S)-norcoclaurine synthase (EC 4.2.1.78 created 1984, modified 1999, deleted 2024)]
Accepted name: etheroleic acid synthase
Reaction: (9Z,11E,13S)-13-hydroperoxy-9,11-octadecadienoate = (9Z,11E)-12-[(1E)-hex-1-en-1-yloxy]dodeca-9,11-dienoate + H2O
Glossary: (9Z,11E)-12-[(1E)-hex-1-en-1-yloxy]dodeca-9,11-dienoic acid = etheroleic acid
(9Z,11E,13S)-13-hydroperoxy-9,11-octadecadienoic acid = 13(S)-HPOD
Other name(s): colneleic acid/etheroleic acid synthase; 13/9-DES; 9/13-DES; 13/9-divinyl ether synthase; (9Z,11E)-12-[(1E)-hex-1-en-1-yloxy]dodeca-9,11-dienoate synthase
Systematic name: (9Z,11E,13S)-13-hydroperoxy-9,11-octadecadienoate lyase
Comments: A heme-thiolate protein (P-450) occurring in several plants, including Allium sativum (garlic) and Selaginella moellendorffii (spikemoss). The enzyme also catalyses the reaction of EC 4.2.1.121, colneleate synthase, to a lesser extent.
References:
1. Grechkin, A.N., Fazliev, F.N. and Mukhtarova, L.S. The lipoxygenase pathway in garlic (Allium sativum L.) bulbs: detection of the novel divinyl ether oxylipins. FEBS Lett. 371 (1995) 159-162. [PMID: 7672118]
2. Stumpe, M., Carsjens, J.G., Gobel, C. and Feussner, I. Divinyl ether synthesis in garlic bulbs. J. Exp. Bot. 59 (2008) 907-915. [PMID: 18326559]
3. Gorina, S.S., Toporkova, Y.Y., Mukhtarova, L.S., Smirnova, E.O., Chechetkin, I.R., Khairutdinov, B.I., Gogolev, Y.V. and Grechkin, A.N. Oxylipin biosynthesis in spikemoss Selaginella moellendorffii: Molecular cloning and identification of divinyl ether synthases CYP74M1 and CYP74M3. Biochim. Biophys Acta 1861 (2016) 301-309. [PMID: 26776054]
Accepted name: α-L-rhamnosyl-(1→4)-D-glucuronate lyase
Reaction: α-L-rhamnosyl-(1→4)-D-glucuronate = L-rhamnopyranose + 4-deoxy-L-threo-hex-4-enopyranuronate
Other name(s): L-rhamnose-α-1,4-D-glucuronate lyase; FoRham (gene name)
Systematic name: α-L-rhamnosyl-(1→4)-D-glucuronate lyase
Comments: The enzyme, characterized from the phytopathogenic fungus Fusarium oxysporum, removes the rhamnosyl residue from α-L-rhamnosyl-(1→4)-D-glucuronate or (with lower activity) from oligosaccharides that contain this motif at the non-reducing end, leaving an unsaturated glucuronate residue. Among its natural substrates is the type II arabinogalactan component of gum arabic.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1. Kondo, T., Kichijo, M., Maruta, A., Nakaya, M., Takenaka, S., Arakawa, T., Fushinobu, S. and Sakamoto, T. Structural and functional analysis of gum arabic L-rhamnose-α-1,4-D-glucuronate lyase establishes a novel polysaccharide lyase family. J. Biol. Chem. 297 (2021) 101001. [PMID: 34303708]
Accepted name: talaropentaene synthase
Reaction: all-trans-hexaprenyl diphosphate = talaropentaene + diphosphate
For diagram of reaction click here
Glossary: talaropentaene = (3aS,5E,9E)-3a,6,10-trimethyl-1-[(2ξ,4E,8E)-undeca-5,9-dien-2-yl]-3,3a,4,7,8,11,12-octahydrocyclopenta[11]annulene
Other name(s): TvTS
Systematic name: pentaprenyl-diphosphate diphosphate-lyase [cyclizing, talaropentaene-forming]
Comments: Isolated from the fungus Talaromyces verruculosus.
References:
1. Tao, H., Lauterbach, L., Bian, G., Chen, R., Hou, A., Mori, T., Cheng, S., Hu, B., Lu, L., Mu, X., Li, M., Adachi, N., Kawasaki, M., Moriya, T., Senda, T., Wang, X., Deng, Z., Abe, I., Dickschat, J.S. and Liu, T. Discovery of non-squalene triterpenes. Nature 606 (2022) 414-419. [PMID: 35650436]
Accepted name: macrophomene synthase
Reaction: all-trans-hexaprenyl diphosphate = macrophomene + diphosphate
For diagram of reaction click here
Glossary: macrophomene = (1S,22R)-tricyclo[20.1.01,22]docosa-2,6,10,14,18-pentaene
Other name(s): MpMS
Systematic name: pentaprenyl-diphosphate diphosphate-lyase [cyclizing, macrophomene-forming]
Comments: Isolated from Macrophomina phaseolina, a pathogenic fungus that causes damping off, seedling blight, collar rot, stem rot, charcoal rot, basal stem rot, and root rot on many plant species. The 22-membered ring in macrophomene represents the largest macrocycle discovered in terpenes so far.
References:
1. Tao, H., Lauterbach, L., Bian, G., Chen, R., Hou, A., Mori, T., Cheng, S., Hu, B., Lu, L., Mu, X., Li, M., Adachi, N., Kawasaki, M., Moriya, T., Senda, T., Wang, X., Deng, Z., Abe, I., Dickschat, J.S. and Liu, T. Discovery of non-squalene triterpenes. Nature 606 (2022) 414-419. [PMID: 35650436]
Accepted name: phomopsene synthase
Reaction: geranylgeranyl diphosphate = phomopsene + diphosphate
For diagram of reaction click here and mechanism click here
Glossary: phomopsene = (1S,6aS,6bR,9aR,10aS)-1,4,7,7,9a-pentamethyl-1,2,3,5,6,6a,6b,7,8,9,9a,10-dodecahydrodicyclopenta[a,d]indene
Other name(s): PaPS; NtPS; NrPS; PmS
Systematic name: geranylgeranyl-diphosphate diphosphate-lyase (cyclizing, phomopsene-formimg)
Comments: A diterpene synthase from the fungus Diaporthe amygdali. Phomopsene synthase has also been isolated from the bacteria Nocardia testacea, Nocardia rhamnosiphila, and Allokutzneria albata. The Allokutzneria albata enzyme also generates allokutznerene (EC 4.2.3.224, allokutznerene synthase), bonnadiene (EC 4.2.3.223, bonnadiene synthase) and traces of (–)-spiroviolene (EC 4.2.3.158, (–)-spiroviolene synthase).
References:
1. Toyomasu, T., Kaneko, A., Tokiwano, T., Kanno, Y., Kanno, Y., Niida, R., Miura, S., Nishioka, T., Ikeda, C., Mitsuhashi, W., Dairi, T., Kawano, T., Oikawa, H., Kato, N. and Sassa, T. Biosynthetic gene-based secondary metabolite screening: a new diterpene, methyl phomopsenonate, from the fungus Phomopsis amygdali. J. Org. Chem. 74 (2009) 1541-1548. [PMID: 19161275]
2. Shinde, S.S., Minami, A., Chen, Z., Tokiwano, T., Toyomasu, T., Kato, N., Sassa, T. and Oikawa, H. Cyclization mechanism of phomopsene synthase: mass spectrometry based analysis of various site-specifically labeled terpenes. J. Antibiot. (Tokyo) 70 (2017) 632-638. [PMID: 28270685]
3. Lauterbach, L., Rinkel, J. and Dickschat, J.S. Two bacterial diterpene synthases from Allokutzneria albata produce bonnadiene, phomopsene, and allokutznerene. Angew. Chem. Int. Ed. Engl. 57 (2018) 8280-8283. [PMID: 29758116]
4. Rinkel, J., Steiner, S.T. and Dickschat, J.S. Diterpene biosynthesis in actinomycetes: studies on cattleyene synthase and phomopsene synthase. Angew. Chem. Int. Ed. Engl. 58 (2019) 9230-9233. [PMID: 31034729]
Accepted name: bonnadiene synthase
Reaction: geranylgeranyl diphosphate = bonnadiene + diphosphate
For diagram of reaction click here and mechanism click here
Glossary: bonnadiene = (1R,7R,7aR,11aR)-1,4,9-trimethyl-7-(propan-2-yl)-2,3,5,6,7,7a,10,11-octahydro-1H-benzo[d]azulene
Other name(s): BdS
Systematic name: geranylgeranyl-diphosphate diphosphate-lyase (cyclizing, bonnadiene-formimg)
Comments: A diterpene synthase isolated from the bacterium Allokutzneria albata. It also generates allokutznerene (EC 4.2.3.224, allokutznerene synthase), phomopsene (EC 4.2.3.222, phomopsene synthase) and traces of (–)-spiroviolene (EC 4.2.3.158, (–)-spiroviolene synthase).
References:
1. Lauterbach, L., Rinkel, J. and Dickschat, J.S. Two bacterial diterpene synthases from Allokutzneria albata produce bonnadiene, phomopsene, and allokutznerene. Angew. Chem. Int. Ed. Engl. 57 (2018) 8280-8283. [PMID: 29758116]
Accepted name: allokutznerene synthase
Reaction: geranylgeranyl diphosphate = allokutznerene + diphosphate
For diagram of reaction click here and mechanism click here
Glossary: allokutznerene = (3S,3aS,7aR,10aR,10bS)-3,6,7a,10,10-pentamethyl-1,2,3,4,5,7,7a,8,9,10,10a,10b-dodecahydrodicyclopenta[d,g]indene
Other name(s): PmS
Systematic name: geranylgeranyl-diphosphate diphosphate-lyase (cyclizing, allokutznerene-formimg)
Comments: A diterpene synthase isolated from the bacterium Allokutzneria albata. It also produces bonnadiene (EC 4.2.3.223, bonnadiene synthase), phomopsene (EC 4.2.3.222, phomopsene synthase) and traces of (–)-spiroviolene (EC 4.2.3.158, (–)-spiroviolene synthase).
References:
1. Lauterbach, L., Rinkel, J. and Dickschat, J.S. Two bacterial diterpene synthases from Allokutzneria albata produce bonnadiene, phomopsene, and allokutznerene. Angew. Chem. Int. Ed. Engl. 57 (2018) 8280-8283. [PMID: 29758116]
Accepted name: cattleyene synthase
Reaction: geranylgeranyl diphosphate = cattleyene + diphosphate
For diagram of reaction click here and mechanism click here
Glossary: cattleyene = (3R,3aS,5aS,5bR,8aR)-3,3a,6,6,8a-pentamethyl-2,3,3a,4,5,5a,5b,6,7,8,8a,9-dodecahydro-1H-pentaleno[2,1-e]indene
Other name(s): CyS
Systematic name: geranylgeranyl-diphosphate diphosphate-lyase (cyclizing, cattleyene-formimg)
Comments: A diterpene synthase isolated from the bacterium Streptantibioticus cattleyicolor.
References:
1. Rinkel, J., Steiner, S.T. and Dickschat, J.S. Diterpene biosynthesis in actinomycetes: studies on cattleyene synthase and phomopsene synthase. Angew. Chem. Int. Ed. Engl. 58 (2019) 9230-9233. [PMID: 31034729]
2. Xing, B., Xu, H., Li, A., Lou, T., Xu, M., Wang, K., Xu, Z., Dickschat, J.S., Yang, D. and Ma, M. Crystal structure based mutagenesis of cattleyene synthase leads to the generation of rearranged polycyclic diterpenes. Angew. Chem. Int. Ed. Engl. 61 (2022) e202209785. [PMID: 35819825]
Accepted name: (+)-2-epi-prezizaene synthase
Reaction: (2Z,6E)-farnesyl diphosphate = (+)-2-epi-prezizaene + diphosphate
Other name(s): EAS3 (gene name); EAS4 (gene name)
Systematic name: (2Z,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, (+)-2-epi-prezizaene-forming)
Comments: The enzyme occurs in plants. The initial cyclization product is a (7R)-β-bisabolyl cation. The major final product is (+)-2-epi-prezizaene. Other products are (-)-α-cedrene (cf. EC 4.2.3.227, (–)-α-cedrene synthase), small amounts of (–)-β-curcumene, and other sesquiterpenes with less than 10% yield. The enzyme also catalyses the reaction of EC 4.2.3.61, 5-epiaristolochene synthase.
References:
1. Noel, J.P., Dellas, N., Faraldos, J.A., Zhao, M., Hess, B.A., Jr., Smentek, L., Coates, R.M. and O'Maille, P.E. Structural elucidation of cisoid and transoid cyclization pathways of a sesquiterpene synthase using 2-fluorofarnesyl diphosphates. ACS Chem. Biol. 5 (2010) 377-392. [PMID: 20175559]
2. Faraldos, J.A., O'Maille, P.E., Dellas, N., Noel, J.P. and Coates, R.M. Bisabolyl-derived sesquiterpenes from tobacco 5-epi-aristolochene synthase-catalyzed cyclization of (2Z,6E)-farnesyl diphosphate. J. Am. Chem. Soc. 132 (2010) 4281-4289. [PMID: 20201526]
Accepted name: (–)-α-cedrene synthase
Reaction: (2Z,6E)-farnesyl diphosphate = (–)-α-cedrene + diphosphate
Other name(s): EAS3 (gene name); EAS4 (gene name)
Systematic name: (2Z,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, (–)-α-cedrene-forming)
Comments: The enzyme occurs in plants. The initial cyclization product is a (7R)-β-bisabolyl cation. (–)-α-Cedrene is one of the major products. Other products are (+)-2-epi-prezizaene (cf. EC 4.2.3.226, (+)-2-epi-prezizaene synthase), small amounts of (+)-β-curcumene, and other sesquiterpenes with less than 10% yield. The enzyme from Nicotiana tabacum (tobacco) also catalyses the reaction of EC 4.2.3.61, 5-epiaristolochene synthase.
References:
1. Noel, J.P., Dellas, N., Faraldos, J.A., Zhao, M., Hess, B.A., Jr., Smentek, L., Coates, R.M. and O'Maille, P.E. Structural elucidation of cisoid and transoid cyclization pathways of a sesquiterpene synthase using 2-fluorofarnesyl diphosphates. ACS Chem. Biol. 5 (2010) 377-392. [PMID: 20175559]
2. Faraldos, J.A., O'Maille, P.E., Dellas, N., Noel, J.P. and Coates, R.M. Bisabolyl-derived sesquiterpenes from tobacco 5-epi-aristolochene synthase-catalyzed cyclization of (2Z,6E)-farnesyl diphosphate. J. Am. Chem. Soc. 132 (2010) 4281-4289. [PMID: 20201526]
Accepted name: (Z)-β-ocimene synthase
Reaction: geranyl diphosphate = (Z)-β-ocimene + diphosphate
For diagram of reaction click here
Glossary: (Z)-β-ocimene = (3Z)-3,7-dimethyl-1,3,6-octatriene
Other name(s): CsTPS13PK (gene name)
Systematic name: geranyl diphosphate diphosphate lyase [(Z)-β-ocimene-forming]
Comments: The enzyme occurs in flowers (pistillate inflorescences) of Cannabis sativa. The enzyme encoded by CsTPS13PK produces 94% (Z)-β-ocimene from geranyl diphosphate. cf. EC 4.2.3.106, (E)-β-ocimene synthase.
References:
1. Booth, J.K., Page, J.E. and Bohlmann, J. Terpene synthases from Cannabis sativa. PLoS One 12 (2017) e0173911. [PMID: 28355238]
Accepted name: ent-beyerene synthase
Reaction: ent-copalyl diphosphate = ent-beyerene + diphosphate
For diagram of reaction click here and mechanism click here
Glossary: ent-beyerene = ent-beyer-15-ene = beyer-15-ene
Other name(s): ent-kaurene synthase like 2; RcKSL4; OsKSL2; PpCPS/KS (ambiguous)
Systematic name: ent-copalyl-diphosphate diphosphate-lyase (cyclizing, ent-beyerene-forming)
Comments: The enzyme has been shown to occur in castor bean (Ricinus communis) and rice (Oryza sativa). ent-Beyerene is also a product of EC 4.2.3.19 (ent-kaurene synthase) of the moss Physcomitrella patens.
References:
1. Jackson, A.J., Hershey, D.M., Chesnut, T., Xu, M. and Peters, R.J. Biochemical characterization of the castor bean ent-kaurene synthase(-like) family supports quantum chemical view of diterpene cyclization. Phytochemistry 103 (2014) 13-21. [PMID: 24810014]
2. Tezuka, D., Ito, A., Mitsuhashi, W., Toyomasu, T. and Imai, R. The rice ent-kaurene synthase like 2 encodes a functional ent-beyerene synthase. Biochem. Biophys. Res. Commun. 460 (2015) 766-771. [PMID: 25824047]
3. Zhan, X., Bach, S.S., Hansen, N.L., Lunde, C. and Simonsen, H.T. Additional diterpenes from Physcomitrella patens synthesized by copalyl diphosphate/kaurene synthase (PpCPS/KS). Plant Physiol. Biochem. 96 (2015) 110-114. [PMID: 26248039]
[EC 4.3.3.2 Transferred entry: strictosidine synthase. Now EC 3.5.99.13, strictosidine synthase (EC 4.3.3.2 created 1990, deleted 2024)]
[EC 4.3.3.3 Transferred entry: deacetylisoipecoside synthase. Now EC 3.5.99.15, deacetylisoipecoside synthase (EC 4.3.3.3 created 2000, deleted 2024)]
[EC 4.3.3.4 Transferred entry: deacetylipecoside synthase. Now EC 3.5.99.16, deacetylipecoside synthase (EC 4.3.3.4 created 2000, deleted 2024)]
Accepted name: hapalindole U synthase
Reaction: 3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole = hapalindole U
For diagram of reaction click here
Glossary: hapalindole U = (6aS,9R,10R,10aS)-10-isocyano-6,6,9-trimethyl-9-vinyl-2,6,6a,7,8,9,10,10a-octahydronaphtho[1,2,3-cd]indole
Other name(s): ambU1/ambU4 (gene names); famC4/famC1 (gene names)
Systematic name: 3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole cyclase (hapalindole U-forming)
Comments: Requires Ca2+. The enzyme, which belongs to the Stig cyclases, has been characterized from multiple species of the cyanobacterial genera Fischerella and Westiellopsis. Stig cyclases catalyse a three step process including a Cope rearrangement, 6-exo-trig cyclization and electrophilic aromatic substitution. The enzyme is a heterodimer of two different proteins (AmbU1 and AmbU4). On their own, AmbU1 catalyses a different reaction, producing 12-epi-hapalindole U (cf. EC 5.5.1.32, 12-epi-hapalindole U synthase) while AmbU4 appears to be inactive. Formation of hapalindole U leads to the biosynthesis of additional terpenoid indole alkaloids such as hapalindole G, ambiguine H, and ambiguine A.
References:
1. Zhu, Q. and Liu, X. Discovery of a calcium-dependent enzymatic cascade for the selective assembly of hapalindole-type alkaloids: on the biosynthetic origin of hapalindole U. Angew. Chem. Int. Ed. Engl. 56 (2017) 9062-9066. [PMID: 28626997]
2. Li, S., Newmister, S.A., Lowell, A.N., Zi, J., Chappell, C.R., Yu, F., Hohlman, R.M., Orjala, J., Williams, R.M. and Sherman, D.H. Control of stereoselectivity in diverse hapalindole metabolites is mediated by cofactor-induced combinatorial pairing of stig cyclases. Angew. Chem. Int. Ed. Engl. 59 (2020) 8166-8172. [PMID: 32052896]
Accepted name: RNA 5'-3' helicase
Reaction: n ATP + n H2O + wound RNA = n ADP + n phosphate + unwound RNA
Other name(s): corona virus helicase nsP13; MOV10; Moloney leukemia virus 10; UPF1; sen1+
Systematic name: RNA 5'-3' helicase (ATP-hydrolysing)
Comments: RNA helicases, which participate in nearly all aspects of RNA metabolism, utilize the energy from ATP hydrolysis to unwind RNA. The engine core of helicases is usually made of a pair of RecA-like domains that form an NTP binding cleft at their interface. Changes in the chemical state of the NTP binding cleft (binding of the NTP or its hydrolysis products) alter the relative positions of the RecA-like domains and nucleic acid-binding domains, creating structural motions that disrupt the pairing of the nucleic acid, causing separation and unwinding. Most RNA helicases utilize a mechanism known as canonical duplex unwinding, in which the helicase binds to a single stranded region adjacent to the duplex and then translocates along the bound strand with defined directionality, displacing the complementary strand. Most of these helicases proceed 3' to 5' (type A polarity - cf. EC 5.6.2.6, RNA 3'-5' helicase), but some proceed 5' to 3' (type B polarity), and some are able to catalyse unwinding in either direction [1,4]. Most canonically operating helicases require substrates with single stranded regions in a defined orientation (polarity) with respect to the duplex. A different class of RNA helicases, EC 5.6.2.7, DEAD-box RNA helicase, use a different mechanism and unwind short stretches of RNA with no translocation.
References:
1. Rozen, F., Edery, I., Meerovitch, K., Dever, T.E., Merrick, W.C. and Sonenberg, N. Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F. Mol. Cell Biol. 10 (1990) 1134-1144. [PMID: 2304461]
2. Kim, H.D., Choe, J. and Seo, Y.S. The sen1(+) gene of Schizosaccharomyces pombe, a homologue of budding yeast SEN1, encodes an RNA and DNA helicase. Biochemistry 38 (1999) 14697-14710. [PMID: 10545196]
3. Bhattacharya, A., Czaplinski, K., Trifillis, P., He, F., Jacobson, A. and Peltz, S.W. Characterization of the biochemical properties of the human Upf1 gene product that is involved in nonsense-mediated mRNA decay. RNA 6 (2000) 1226-1235. [PMID: 10999600]
4. Lee, C.G. RH70, a bidirectional RNA helicase, co-purifies with U1snRNP. J. Biol. Chem. 277 (2002) 39679-39683. [PMID: 12193588]
5. Gregersen, L.H., Schueler, M., Munschauer, M., Mastrobuoni, G., Chen, W., Kempa, S., Dieterich, C. and Landthaler, M. MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA target degradation by translocation along 3' UTRs. Mol. Cell 54 (2014) 573-585. [PMID: 24726324]
6. Jang, K.J., Jeong, S., Kang, D.Y., Sp, N., Yang, Y.M. and Kim, D.E. A high ATP concentration enhances the cooperative translocation of the SARS coronavirus helicase nsP13 in the unwinding of duplex RNA. Sci. Rep. 10 (2020) 4481. [PMID: 32161317]
Accepted name: RNA 3'-5' helicase
Reaction: n ATP + n H2O + wound RNA = n ADP + n phosphate + unwound RNA
Other name(s): DEAH/RHA protein; DEAH-box protein 2; Prp22p; DHX8; DHX36; CSFV NS3 helicase; nonstructural protein 3 helicase; KOKV helicase; Kokobera virus helicase; hepatitis C virus NS3 protein; DExH protein; MTR4; SKI2; BRR2; SUV3; Rig-I; retinoic-acid-inducible gene I; DbpA
Systematic name: RNA 3'-5' helicase (ATP-hydrolysing)
Comments: RNA helicases, which participate in nearly all aspects of RNA metabolism, utilize the energy from ATP hydrolysis to unwind RNA. The engine core of helicases is usually made of a pair of RecA-like domains that form an NTP binding cleft at their interface. Changes in the chemical state of the NTP binding cleft (binding of the NTP or its hydrolysis products) alter the relative positions of the RecA-like domains and nucleic acid-binding domains, creating structural motions that disrupt the pairing of the nucleic acid, causing separation and unwinding. Most RNA helicases utilize a mechanism known as canonical duplex unwinding, in which the helicase binds to a single stranded region adjacent to the duplex and then translocates along the bound strand with defined directionality, displacing the complementary strand. Most of these helicases proceed 3' to 5' (type A polarity), but some proceed 5' to 3' (type B polarity - cf. EC 5.6.2.5, RNA 5'-3' helicase), and some are able to catalyse unwinding in either direction [1,3]. Most canonically operating helicases require substrates with single stranded regions in a defined orientation (polarity) with respect to the duplex. A different class of RNA helicases, EC 5.6.2.7, DEAD-box RNA helicase, use a different mechanism and unwind short stretches of RNA with no translocation.
References:
1. Rozen, F., Edery, I., Meerovitch, K., Dever, T.E., Merrick, W.C. and Sonenberg, N. Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F. Mol. Cell Biol. 10 (1990) 1134-1144. [PMID: 2304461]
2. Shuman, S. Vaccinia virus RNA helicase. Directionality and substrate specificity. J. Biol. Chem. 268 (1993) 11798-11802. [PMID: 8505308]
3. Lee, C.G. RH70, a bidirectional RNA helicase, co-purifies with U1snRNP. J. Biol. Chem. 277 (2002) 39679-39683. [PMID: 12193588]
4. Zhang, S. and Grosse, F. Multiple functions of nuclear DNA helicase II (RNA helicase A) in nucleic acid metabolism. Acta Biochim Biophys Sin (Shanghai) 36 (2004) 177-183. [PMID: 15202501]
5. Diges, C.M. and Uhlenbeck, O.C. Escherichia coli DbpA is a 3' → 5' RNA helicase. Biochemistry 44 (2005) 7903-7911. [PMID: 15910005]
6. Frick, D.N. The hepatitis C virus NS3 protein: a model RNA helicase and potential drug target. Curr. Issues Mol. Biol. 9 (2007) 1-20. [PMID: 17263143]
7. Schwer, B. A conformational rearrangement in the spliceosome sets the stage for Prp22-dependent mRNA release. Mol. Cell 30 (2008) 743-754. [PMID: 18570877]
8. Takahasi, K., Yoneyama, M., Nishihori, T., Hirai, R., Kumeta, H., Narita, R., Gale, M., Jr., Inagaki, F. and Fujita, T. Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses. Mol. Cell 29 (2008) 428-440. [PMID: 18242112]
9. Wang, X., Jia, H., Jankowsky, E. and Anderson, J.T. Degradation of hypomodified tRNA(iMet) in vivo involves RNA-dependent ATPase activity of the DExH helicase Mtr4p. RNA 14 (2008) 107-116. [PMID: 18000032]
10. Wen, G., Xue, J., Shen, Y., Zhang, C. and Pan, Z. Characterization of classical swine fever virus (CSFV) nonstructural protein 3 (NS3) helicase activity and its modulation by CSFV RNA-dependent RNA polymerase. Virus Res. 141 (2009) 63-70. [PMID: 19185595]
Accepted name: DEAD-box RNA helicase
Reaction: ATP + H2O + wound RNA = ADP + phosphate + unwound RNA
Other name(s): Dbp2; DDX3; DDX4; DDX5; DDX17; DDX3Y; RM62; hDEAD1; RNA helicase Hera; DED1
Systematic name: RNA helicase (non-translocating)
Comments: RNA helicases, which participate in nearly all aspects of RNA metabolism, utilize the energy from ATP hydrolysis to unwind RNA. The engine core of helicases is usually made of a pair of RecA-like domains that form an NTP binding cleft at their interface. Changes in the chemical state of the NTP binding cleft (binding of the NTP or its hydrolysis products) alter the relative positions of the RecA-like domains and nucleic acid-binding domains, creating structural motions that disrupt the pairing of the nucleic acid, causing separation and unwinding. While most RNA helicases utilize a mechanism known as canonical duplex unwinding and translocate along the RNA (cf. EC 5.6.2.5, RNA 5'-3' helicase and EC 5.6.2.6, RNA 3'-5' helicase), DEAD-box RNA helicases differ by unwinding RNA via the local strand separation mechanism, which does not involve translocation. These helicases load directly on the duplex region, aided by single stranded or structured nucleic acid regions. Upon loading, the DEAD-box protein locally opens the duplex strands. This step requires binding of ATP, which is not hydrolysed. The local helix opening causes the remaining basepairs to dissociate without further action from the enzyme. Unwinding occurs without apparent polarity, and is limited to relatively short distances. ATP hydrolysis is required for release of the DEAD-box protein from the RNA. The name originates from the sequence D-E-A-D, which is found in Motif II of these proteins.
References:
1. Linder, P., Lasko, P.F., Ashburner, M., Leroy, P., Nielsen, P.J., Nishi, K., Schnier, J. and Slonimski, P.P. Birth of the D-E-A-D box. Nature 337 (1989) 121-122. [PMID: 2563148]
2. Tang, P.Z., Tsai-Morris, C.H. and Dufau, M.L. A novel gonadotropin-regulated testicular RNA helicase. A new member of the dead-box family. J. Biol. Chem. 274 (1999) 37932-37940. [PMID: 10608860]
3. Rossler, O.G., Straka, A. and Stahl, H. Rearrangement of structured RNA via branch migration structures catalysed by the highly related DEAD-box proteins p68 and p72. Nucleic Acids Res. 29 (2001) 2088-2096. [PMID: 11353078]
4. Bizebard, T., Ferlenghi, I., Iost, I. and Dreyfus, M. Studies on three E. coli DEAD-box helicases point to an unwinding mechanism different from that of model DNA helicases. Biochemistry 43 (2004) 7857-7866. [PMID: 15196029]
5. Garbelli, A., Beermann, S., Di Cicco, G., Dietrich, U. and Maga, G. A motif unique to the human DEAD-box protein DDX3 is important for nucleic acid binding, ATP hydrolysis, RNA/DNA unwinding and HIV-1 replication. PLoS One 6 (2011) e19810. [PMID: 21589879]
6. Jarmoskaite, I. and Russell, R. DEAD-box proteins as RNA helicases and chaperones. Wiley Interdiscip Rev RNA 2 (2011) 135-152. [PMID: 21297876]
7. Linder, P. and Fuller-Pace, F.V. Looking back on the birth of DEAD-box RNA helicases. Biochim. Biophys Acta 1829 (2013) 750-755. [PMID: 23542735]
Accepted name: putrebactin synthase
Reaction: 2 ATP + 2 N1-hydroxy-N1-succinylputrescine = 2 AMP + 2 diphosphate + putrebactin (overall reaction)
(1a) ATP + 2 N1-hydroxy-N1-succinylputrescine = AMP + diphosphate + pre-putrebactin
(1b) ATP + pre-putrebactin = AMP + diphosphate + putrebactin
For diagram of reaction click here
Glossary: putrebactin = 1,11-dihydroxy-1,6,11,16-tetraazacycloicosane-2,5,12,15-tetrone
pre-putrebactin = 4-{[4-({4-[(4-aminobutyl)(hydroxy)amino]-4-oxobutanoyl}amino)butyl](hydroxy)amino}-4-oxobutanoate
Other name(s): pubC (gene name)
Systematic name: N1-hydroxy-N1-succinylputrescine:N1-hydroxy-N1-succinylputrescine ligase
Comments: Requires Mg2+. The enzyme, characterized from the bacteria Shewanella spp. MR-4 and MR-7, catalyse the last step in the biosynthesis of the siderophore putrebactin. The enzyme catalyses the reaction in two steps - concatenation of two molecules of N1-hydroxy-N1-succinylputrescine, followed by cyclization.
References:
1. Kadi, N., Arbache, S., Song, L., Oves-Costales, D. and Challis, G.L. Identification of a gene cluster that directs putrebactin biosynthesis in Shewanella species: PubC catalyzes cyclodimerization of N-hydroxy-N-succinylputrescine. J. Am. Chem. Soc. 130 (2008) 10458-10459. [PMID: 18630910]
Accepted name: bisucaberin synthase
Reaction: 2 ATP + 2 N1-hydroxy-N1-succinylcadaverine = 2 AMP + 2 diphosphate + bisucaberin (overall reaction)
(1a) ATP + 2 N1-hydroxy-N1-succinylcadaverine = AMP + diphosphate + bisucaberin B
(1b) ATP + bisucaberin B = AMP + diphosphate + bisucaberin
Glossary: bisucaberin B = pre-bisucaberin = 3-[(5-{3-[(5-aminopentyl)(hydroxy)carbamoyl]propanamido}pentyl)(hydroxy)carbamoyl]propanoate
bisucaberin = 1,12-dihydroxy-1,6,12,17-tetrazacyclodocosane-2,5,13,16-tetrone
Other name(s): pubC (gene name); BibC C-terminal domain
Systematic name: N1-hydroxy-N1-succinylcadaverine:N1-hydroxy-N1-succinylcadaverine ligase
Comments: Requires Mg2+. The enzyme, characterized from the bacterium Aliivibrio salmonicida, catalyses the last step in the biosynthesis of the siderophore bisucaberin. The enzyme catalyses the reaction in two steps - concatenation of two molecules of N1-hydroxy-N1-succinylcadaverine, followed by cyclization.
References:
1. Kadi, N., Song, L. and Challis, G.L. Bisucaberin biosynthesis: an adenylating domain of the BibC multi-enzyme catalyzes cyclodimerization of N-hydroxy-N-succinylcadaverine. Chem. Commun. (Camb.) (2008) 5119-5121. [PMID: 18956041]
Accepted name: tetrahydromethanopterin S-methyltransferase
Reaction: 5-methyl-5,6,7,8-tetrahydromethanopterin + CoM + 2 Na+[side 1] = 5,6,7,8-tetrahydromethanopterin + 2-(methylsulfanyl)ethane-1-sulfonate + 2 Na+[side 2]
For diagram of reaction click here
Glossary: CoM = coenzyme M = 2-sulfanylethane-1-sulfonate
tetrahydromethanopterin = 1-(4-{(1R)-1-[(6S,7S)-2-amino-7-methyl-4-oxo-3,4,5,6,7,8-hexahydropteridin-6-yl]ethylamino}phenyl)-1-deoxy-5-O-{5-O-[(1S)-1,3-dicarboxypropylphosphonato]-α-D-ribofuranosyl}-D-ribitol
Other name(s): tetrahydromethanopterin methyltransferase; mtrA-H (gene names); cmtA (gene name); N5-methyltetrahydromethanopterin—coenzyme M methyltransferase; 5-methyl-5,6,7,8-tetrahydromethanopterin:2-mercaptoethanesulfonate 2-methyltransferase
Systematic name: 5-methyl-5,6,7,8-tetrahydromethanopterin:CoM 2-methyltransferase (Na+-transporting)
Comments: Involved in the formation of methane from CO2 in methanogenic archaea. The reaction involves the export of one or two sodium ions. The enzyme from the archaeon Methanobacterium thermoautotrophicum is a membrane-associated multienzyme complex composed of eight different subunits, and contains a 5'-hydroxybenzimidazolyl-cobamide cofactor, to which the methyl group is attached during the transfer. A soluble enzyme that is induced by the presence of CO has been reported as well [6].
References:
1. Sauer, F.D. Tetrahydromethanopterin methyltransferase, a component of the methane synthesizing complex of Methanobacterium thermoautotrophicum. Biochem. Biophys. Res. Commun. 136 (1986) 542-547. [PMID: 3085670]
2. Gartner, P., Ecker, A., Fischer, R., Linder, D., Fuchs, G. and Thauer, R.K. Purification and properties of N5-methyltetrahydromethanopterin:coenzyme M methyltransferase from Methanobacterium thermoautotrophicum. Eur. J. Biochem. 213 (1993) 537-545. [PMID: 8477726]
3. Weiss, D.S., Gartner, P. and Thauer, R.K. The energetics and sodium-ion dependence of N5-methyltetrahydromethanopterin:coenzyme M methyltransferase studied with cob(I)alamin as methyl acceptor and methylcob(III)alamin as methyl donor. Eur. J. Biochem. 226 (1994) 799-809. [PMID: 7813469]
4. Harms, U., Weiss, D.S., Gartner, P., Linder, D. and Thauer, R.K. The energy conserving N5-methyltetrahydromethanopterin:coenzyme M methyltransferase complex from Methanobacterium thermoautotrophicum is composed of eight different subunits. Eur. J. Biochem. 228 (1995) 640-648. [PMID: 7737157]
5. Gottschalk, G. and Thauer, R.K. The Na+-translocating methyltransferase complex from methanogenic archaea. Biochim. Biophys. Acta 1505 (2001) 28-36. [PMID: 11248186]
6. Vepachedu, V.R. and Ferry, J.G. Role of the fused corrinoid/methyl transfer protein CmtA during CO-dependent growth of Methanosarcina acetivorans. J. Bacteriol. 194 (2012) 4161-4168. [PMID: 22636775]