EC |
6.3.2.20 |
Accepted name: |
indoleacetate—lysine synthetase |
Reaction: |
ATP + (indol-3-yl)acetate + L-lysine = ADP + phosphate + N6-[(indol-3-yl)acetyl]-L-lysine |
Other name(s): |
indoleacetate:L-lysine ligase (ADP-forming) |
Systematic name: |
(indol-3-yl)acetate:L-lysine ligase (ADP-forming) |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 103537-15-1 |
References: |
1. |
Glass, N.L. and Kosuge, T. Cloning of the gene for indoleacetic acid-lysine synthetase from Pseudomonas syringae subsp. savastanoi. J. Bacteriol. 166 (1986) 598. [DOI] [PMID: 3084452] |
2. |
Hutzinger, O. and Kosuge, T. Microbial synthesis and degradation of indole-3-acetic acid. 3. The isolation and characterization of indole-3-acetyl-ε-L-lysine. Biochemistry 7 (1968) 601–605. [PMID: 5644130] |
|
[EC 6.3.2.20 created 1989] |
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|
EC
|
6.3.2.21
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Deleted entry: | ubiquitin—calmodulin ligase. The reaction is performed by the sequential action of EC 6.2.1.45 (ubiquitin-activating enzyme E1), several ubiquitin transferases and finally by EC 2.3.2.27 [ubiquitin transferase RING E3 (calmodulin-selective)] |
[EC 6.3.2.21 created 1990, deleted 2015] |
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EC
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6.3.2.22
|
Transferred entry: | diphthine—ammonia ligase. Now EC 6.3.1.14, diphthine—ammonia ligase.
|
[EC 6.3.2.22 created 1990, deleted 2010] |
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|
EC |
6.3.2.23 |
Accepted name: |
homoglutathione synthase |
Reaction: |
ATP + γ-L-glutamyl-L-cysteine + β-alanine = ADP + phosphate + γ-L-glutamyl-L-cysteinyl-β-alanine |
Other name(s): |
homoglutathione synthetase; β-alanine specific hGSH synthetase |
Systematic name: |
γ-L-glutamyl-L-cysteine:β-alanine ligase (ADP-forming) |
Comments: |
Not identical with EC 6.3.2.3 glutathione synthase. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 113875-72-2 |
References: |
1. |
Macnicol, P.K. Homoglutathione and glutathione synthetases of legume seedlings - partial-purification and substrate-specificity. Plant Sci. 53 (1987) 229–235. |
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[EC 6.3.2.23 created 1990] |
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EC |
6.3.2.24 |
Accepted name: |
tyrosine—arginine ligase |
Reaction: |
ATP + L-tyrosine + L-arginine = AMP + diphosphate + L-tyrosyl-L-arginine |
Other name(s): |
tyrosyl-arginine synthase; kyotorphin synthase; kyotorphin-synthesizing enzyme; kyotorphin synthetase |
Systematic name: |
L-tyrosine:L-arginine ligase (AMP-forming) |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 116036-78-3 |
References: |
1. |
Ueda, H., Yoshihara, Y., Fukushima, N., Shiomi, H., Nakamura, A. and Takagi, H. Kyotorphin (tyrosine-arginine) synthetase in rat brain synaptosomes. J. Biol. Chem. 262 (1987) 8165–8173. [PMID: 3597366] |
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[EC 6.3.2.24 created 1992] |
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EC |
6.3.2.25 |
Accepted name: |
tubulin—tyrosine ligase |
Reaction: |
ATP + detyrosinated α-tubulin + L-tyrosine = α-tubulin + ADP + phosphate |
Systematic name: |
α-tubulin:L-tyrosine ligase (ADP-forming) |
Comments: |
L-Tyrosine is linked via a peptide bond to the C-terminus of de-tyrosinated α-tubulin (des-Tyrω-α-tubulin). The enzyme is highly specific for α-tubulin and moderately specific for ATP and L-tyrosine. L-Phenylalanine and 3,4-dihydroxy-L-phenylalanine are transferred but with higher Km values. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 60321-03-1 |
References: |
1. |
Wehland, J., Schröder, H.C., Weber, K. Isolation and purification of tubulin-tyrosine ligase. Methods Enzymol. 134 (1986) 170–179. [PMID: 3821560] |
2. |
Rudiger, M., Wehland, J., Weber, K. The carboxy-terminal peptide of detyrosinated α tubulin provides a minimal system to study the substrate specificity of tubulin-tyrosine ligase. Eur. J. Biochem. 220 (1994) 309–320. [DOI] [PMID: 7510228] |
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[EC 6.3.2.25 created 1999] |
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EC |
6.3.2.26 |
Accepted name: |
N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase |
Reaction: |
3 ATP + L-2-aminohexanedioate + L-cysteine + L-valine + H2O = 3 AMP + 3 diphosphate + N-[L-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine |
|
For diagram of penicillin-N and deacetoxycephalosporin-C biosynthesis, click here and for possible mechanism of reaction, click here |
Other name(s): |
L-δ-(α-aminoadipoyl)-L-cysteinyl-D-valine synthetase; ACV synthetase; L-α-aminoadipyl-cysteinyl-valine synthetase; |
Systematic name: |
L-2-aminohexanedioate:L-cysteine:L-valine ligase (AMP-forming, valine-inverting) |
Comments: |
Requires Mg2+. The enzyme contains 4′-phosphopantetheine, which may be involved in the mechanism of the reaction. Forms part of the penicillin biosynthesis pathway (for pathway, click here). |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 57219-73-5 |
References: |
1. |
Byford, M.F., Baldwin, J.E., Shiau, C.-Y. and Schofield, C.J. The mechanism of ACV synthetase. Chem. Rev. 97 (1997) 2631–2649. [DOI] [PMID: 11851475] |
2. |
Theilgaard, H.B., Kristiansen, K.N., Henriksen, C.M. and Nielsen, J. Purification and characterization of δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine synthetase from Penicillium chrysogenum. Biochem. J. 327 (1997) 185–191. [PMID: 9355751] |
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[EC 6.3.2.26 created 2002] |
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EC
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6.3.2.27
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Deleted entry: | The activity is covered by two independent enzymes, EC 6.3.2.38 N2-citryl-N6-acetyl-N6-hydroxylysine synthase, and EC 6.3.2.39, aerobactin synthase |
[EC 6.3.2.27 created 2002, modified 2006, deleted 2012] |
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EC
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6.3.2.28
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Transferred entry: | L-amino-acid α-ligase. Now EC 6.3.2.49, L-alanine-L-anticapsin ligase
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[EC 6.3.2.28 created 2006, deleted 2015] |
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EC |
6.3.2.29 |
Accepted name: |
cyanophycin synthase (L-aspartate-adding) |
Reaction: |
ATP + [L-Asp(4-L-Arg)]n + L-Asp = ADP + phosphate + [L-Asp(4-L-Arg)]n-L-Asp |
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For diagram of cyanophycin biosynthesis, click here |
Glossary: |
cyanophycin = [L-Asp(4-L-Arg)]n = N-β-aspartylarginine = [L-4-(L-arginin-2-N-yl)aspartic acid]n = poly{N4-[(1S)-1-carboxy-4-guanidinobutyl]-L-asparagine} |
Other name(s): |
CphA (ambiguous); CphA1 (ambiguous); CphA2 (ambiguous); cyanophycin synthetase (ambiguous); multi-L-arginyl-poly-L-aspartate synthase (ambiguous) |
Systematic name: |
cyanophycin:L-aspartate ligase (ADP-forming) |
Comments: |
Requires Mg2+ for activity. Both this enzyme and EC 6.3.2.30, cyanophycin synthase (L-arginine-adding), are required for the elongation of cyanophycin, which is a protein-like cell inclusion that is unique to cyanobacteria and acts as a temporary nitrogen store [2]. Both enzymes are found in the same protein but have different active sites [2,4]. Both L-Asp and L-Arg must be present before either enzyme will display significant activity [2]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 131554-17-1 |
References: |
1. |
Aboulmagd, E., Oppermann-Sanio, F.B. and Steinbüchel, A. Molecular characterization of the cyanophycin synthetase from Synechocystis sp. strain PCC6308. Arch. Microbiol. 174 (2000) 297–306. [PMID: 11131019] |
2. |
Aboulmagd, E., Oppermann-Sanio, F.B. and Steinbüchel, A. Purification of Synechocystis sp. strain PCC6308 cyanophycin synthetase and its characterization with respect to substrate and primer specificity. Appl. Environ. Microbiol. 67 (2001) 2176–2182. [DOI] [PMID: 11319097] |
3. |
Allen, M.M., Hutchison, F. and Weathers, P.J. Cyanophycin granule polypeptide formation and degradation in the cyanobacterium Aphanocapsa 6308. J. Bacteriol. 141 (1980) 687–693. [PMID: 6767688] |
4. |
Berg, H., Ziegler, K., Piotukh, K., Baier, K., Lockau, W. and Volkmer-Engert, R. Biosynthesis of the cyanobacterial reserve polymer multi-L-arginyl-poly-L-aspartic acid (cyanophycin): mechanism of the cyanophycin synthetase reaction studied with synthetic primers. Eur. J. Biochem. 267 (2000) 5561–5570. [DOI] [PMID: 10951215] |
5. |
Ziegler, K., Deutzmann, R. and Lockau, W. Cyanophycin synthetase-like enzymes of non-cyanobacterial eubacteria: characterization of the polymer produced by a recombinant synthetase of Desulfitobacterium hafniense. Z. Naturforsch. [C] 57 (2002) 522–529. [PMID: 12132696] |
6. |
Ziegler, K., Diener, A., Herpin, C., Richter, R., Deutzmann, R. and Lockau, W. Molecular characterization of cyanophycin synthetase, the enzyme catalyzing the biosynthesis of the cyanobacterial reserve material multi-L-arginyl-poly-L-aspartate (cyanophycin). Eur. J. Biochem. 254 (1998) 154–159. [DOI] [PMID: 9652408] |
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[EC 6.3.2.29 created 2007] |
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EC |
6.3.2.30 |
Accepted name: |
cyanophycin synthase (L-arginine-adding) |
Reaction: |
ATP + [L-Asp(4-L-Arg)]n-L-Asp + L-Arg = ADP + phosphate + [L-Asp(4-L-Arg)]n+1 |
|
For diagram of cyanophycin biosynthesis, click here |
Glossary: |
cyanophycin = [L-Asp(4-L-Arg)]n = N-β-aspartylarginine = [L-4-(L-arginin-2-N-yl)aspartic acid]n = poly{N4-[(1S)-1-carboxy-4-guanidinobutyl]-L-asparagine} |
Other name(s): |
CphA (ambiguous); CphA1 (ambiguous); CphA2 (ambiguous); cyanophycin synthetase (ambiguous); multi-L-arginyl-poly-L-aspartate synthase (ambiguous) |
Systematic name: |
cyanophycin:L-arginine ligase (ADP-forming) |
Comments: |
Requires Mg2+ for activity. Both this enzyme and EC 6.3.2.29, cyanophycin synthase (L-aspartate-adding), are required for the elongation of cyanophycin, which is a protein-like cell inclusion that is unique to cyanobacteria and acts as a temporary nitrogen store [2]. Both enzymes are found in the same protein but have different active sites [2,4]. Both L-Asp and L-Arg must be present before either enzyme will display significant activity [2]. Canavanine and lysine can be incoporated into the polymer instead of arginine [2]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 131554-17-1 |
References: |
1. |
Aboulmagd, E., Oppermann-Sanio, F.B. and Steinbüchel, A. Molecular characterization of the cyanophycin synthetase from Synechocystis sp. strain PCC6308. Arch. Microbiol. 174 (2000) 297–306. [PMID: 11131019] |
2. |
Aboulmagd, E., Oppermann-Sanio, F.B. and Steinbüchel, A. Purification of Synechocystis sp. strain PCC6308 cyanophycin synthetase and its characterization with respect to substrate and primer specificity. Appl. Environ. Microbiol. 67 (2001) 2176–2182. [DOI] [PMID: 11319097] |
3. |
Allen, M.M., Hutchison, F. and Weathers, P.J. Cyanophycin granule polypeptide formation and degradation in the cyanobacterium Aphanocapsa 6308. J. Bacteriol. 141 (1980) 687–693. [PMID: 6767688] |
4. |
Berg, H., Ziegler, K., Piotukh, K., Baier, K., Lockau, W. and Volkmer-Engert, R. Biosynthesis of the cyanobacterial reserve polymer multi-L-arginyl-poly-L-aspartic acid (cyanophycin): mechanism of the cyanophycin synthetase reaction studied with synthetic primers. Eur. J. Biochem. 267 (2000) 5561–5570. [DOI] [PMID: 10951215] |
5. |
Ziegler, K., Deutzmann, R. and Lockau, W. Cyanophycin synthetase-like enzymes of non-cyanobacterial eubacteria: characterization of the polymer produced by a recombinant synthetase of Desulfitobacterium hafniense. Z. Naturforsch. [C] 57 (2002) 522–529. [PMID: 12132696] |
6. |
Ziegler, K., Diener, A., Herpin, C., Richter, R., Deutzmann, R. and Lockau, W. Molecular characterization of cyanophycin synthetase, the enzyme catalyzing the biosynthesis of the cyanobacterial reserve material multi-L-arginyl-poly-L-aspartate (cyanophycin). Eur. J. Biochem. 254 (1998) 154–159. [DOI] [PMID: 9652408] |
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[EC 6.3.2.30 created 2007] |
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EC |
6.3.2.31 |
Accepted name: |
coenzyme F420-0:L-glutamate ligase |
Reaction: |
GTP + coenzyme F420-0 + L-glutamate = GDP + phosphate + coenzyme F420-1 |
|
For diagram of coenzyme F420 biosynthesis, click here |
Glossary: |
coenzyme F420 = N-(N-{O-[5-(8-hydroxy-2,4-dioxo-2,3,4,10-tetrahydropyrimido[4,5-b]quinolin-10-yl)-5-deoxy-L-ribityl-1-phospho]-(S)-lactyl}-γ-L-glutamyl)-L-glutamate |
Other name(s): |
CofE-AF; MJ0768; CofE |
Systematic name: |
L-glutamate:coenzyme F420-0 ligase (GDP-forming) |
Comments: |
This protein catalyses the successive addition of two glutamate residues to factor F420 (coenzyme F420) by two distinct and independent reactions. In the reaction described here the enzyme attaches a glutamate via its α-amine group to F420-0. In the second reaction (EC 6.3.2.34, coenzyme F420-1:γ-L-glutamate ligase) it catalyses the addition of a second L-glutamate residue to the γ-carboxyl of the first glutamate. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Li, H., Graupner, M., Xu, H. and White, R.H. CofE catalyzes the addition of two glutamates to F420-0 in F420 coenzyme biosynthesis in Methanococcus jannaschii. Biochemistry 42 (2003) 9771–9778. [DOI] [PMID: 12911320] |
2. |
Nocek, B., Evdokimova, E., Proudfoot, M., Kudritska, M., Grochowski, L.L., White, R.H., Savchenko, A., Yakunin, A.F., Edwards, A. and Joachimiak, A. Structure of an amide bond forming F420:γ-glutamyl ligase from Archaeoglobus fulgidus — a member of a new family of non-ribosomal peptide synthases. J. Mol. Biol. 372 (2007) 456–469. [DOI] [PMID: 17669425] |
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[EC 6.3.2.31 created 2010] |
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EC |
6.3.2.32 |
Accepted name: |
coenzyme γ-F420-2:α-L-glutamate ligase |
Reaction: |
ATP + coenzyme γ-F420-2 + L-glutamate = ADP + phosphate + coenzyme α-F420-3 |
|
For diagram of coenzyme F420 biosynthesis, click here |
Other name(s): |
MJ1001; CofF protein; γ-F420-2:α-L-glutamate ligase |
Systematic name: |
L-glutamate:coenzyme γ-F420-2 (ADP-forming) |
Comments: |
The enzyme caps the γ-glutamyl tail of the hydride carrier coenzyme F420 [1]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Li, H., Xu, H., Graham, D.E. and White, R.H. Glutathione synthetase homologs encode α-L-glutamate ligases for methanogenic coenzyme F420 and tetrahydrosarcinapterin biosyntheses. Proc. Natl. Acad. Sci. USA 100 (2003) 9785–9790. [DOI] [PMID: 12909715] |
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[EC 6.3.2.32 created 2010] |
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EC |
6.3.2.33 |
Accepted name: |
tetrahydrosarcinapterin synthase |
Reaction: |
ATP + tetrahydromethanopterin + L-glutamate = ADP + phosphate + 5,6,7,8-tetrahydrosarcinapterin |
|
For diagram of methanopterin biosynthesis (part 4), click here |
Other name(s): |
H4MPT:α-L-glutamate ligase; MJ0620; MptN protein |
Systematic name: |
tetrahydromethanopterin:α-L-glutamate ligase (ADP-forming) |
Comments: |
This enzyme catalyses the biosynthesis of 5,6,7,8-tetrahydrosarcinapterin, a modified form of tetrahydromethanopterin found in the Methanosarcinales. It does not require K+, and does not discriminate between ATP and GTP [1]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Li, H., Xu, H., Graham, D.E. and White, R.H. Glutathione synthetase homologs encode α-L-glutamate ligases for methanogenic coenzyme F420 and tetrahydrosarcinapterin biosyntheses. Proc. Natl. Acad. Sci. USA 100 (2003) 9785–9790. [DOI] [PMID: 12909715] |
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[EC 6.3.2.33 created 2010] |
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EC |
6.3.2.34 |
Accepted name: |
coenzyme F420-1:γ-L-glutamate ligase |
Reaction: |
GTP + coenzyme F420-1 + L-glutamate = GDP + phosphate + coenzyme γ-F420-2 |
|
For diagram of coenzyme F420 biosynthesis, click here |
Glossary: |
coenzyme F420 = N-(N-{O-[5-(8-hydroxy-2,4-dioxo-2,3,4,10-tetrahydropyrimido[4,5-b]quinolin-10-yl)-5-deoxy-L-ribityl-1-phospho]-(S)-lactyl}-γ-L-glutamyl)-L-glutamate |
Other name(s): |
F420:γ-glutamyl ligase; CofE-AF; MJ0768; CofE |
Systematic name: |
L-glutamate:coenzyme F420-1 ligase (GDP-forming) |
Comments: |
This protein catalyses the successive addition of two glutamate residues to factor 420 (coenzyme F420) by two distinct and independent reactions. In the first reaction (EC 6.3.2.31, coenzyme F420-0:L-glutamate ligase) the enzyme attaches a glutamate via its α-amine group to F420-0. In the second reaction, which is described here, the enzyme catalyses the addition of a second L-glutamate residue to the γ-carboxyl of the first glutamate. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Li, H., Graupner, M., Xu, H. and White, R.H. CofE catalyzes the addition of two glutamates to F420-0 in F420 coenzyme biosynthesis in Methanococcus jannaschii. Biochemistry 42 (2003) 9771–9778. [DOI] [PMID: 12911320] |
2. |
Nocek, B., Evdokimova, E., Proudfoot, M., Kudritska, M., Grochowski, L.L., White, R.H., Savchenko, A., Yakunin, A.F., Edwards, A. and Joachimiak, A. Structure of an amide bond forming F420:γ-glutamyl ligase from Archaeoglobus fulgidus — a member of a new family of non-ribosomal peptide synthases. J. Mol. Biol. 372 (2007) 456–469. [DOI] [PMID: 17669425] |
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[EC 6.3.2.34 created 2010, modified 2023] |
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EC |
6.3.2.35 |
Accepted name: |
D-alanine—D-serine ligase |
Reaction: |
D-alanine + D-serine + ATP = D-alanyl-D-serine + ADP + phosphate |
Other name(s): |
VanC; VanE; VanG |
Systematic name: |
D-alanine:D-serine ligase (ADP-forming) |
Comments: |
The product of this enzyme, D-alanyl-D-serine, can be incorporated into the peptidoglycan pentapeptide instead of the usual D-alanyl-D-alanine dipeptide, which is formed by EC 6.3.2.4, D-alanine—D-alanine ligase. The resulting peptidoglycan does not bind the glycopeptide antibiotics vancomycin and teicoplanin, conferring resistance on the bacteria. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Dutka-Malen, S., Molinas, C., Arthur, M. and Courvalin, P. Sequence of the vanC gene of Enterococcus gallinarum BM4174 encoding a D-alanine:D-alanine ligase-related protein necessary for vancomycin resistance. Gene 112 (1992) 53–58. [DOI] [PMID: 1551598] |
2. |
Park, I.S., Lin, C.H. and Walsh, C.T. Bacterial resistance to vancomycin: overproduction, purification, and characterization of VanC2 from Enterococcus casseliflavus as a D-Ala-D-Ser ligase. Proc. Natl. Acad. Sci. USA 94 (1997) 10040–10044. [DOI] [PMID: 9294159] |
3. |
Fines, M., Perichon, B., Reynolds, P., Sahm, D.F. and Courvalin, P. VanE, a new type of acquired glycopeptide resistance in Enterococcus faecalis BM4405. Antimicrob. Agents Chemother. 43 (1999) 2161–2164. [PMID: 10471558] |
4. |
Depardieu, F., Bonora, M.G., Reynolds, P.E. and Courvalin, P. The vanG glycopeptide resistance operon from Enterococcus faecalis revisited. Mol. Microbiol. 50 (2003) 931–948. [DOI] [PMID: 14617152] |
5. |
Watanabe, S., Kobayashi, N., Quinones, D., Hayakawa, S., Nagashima, S., Uehara, N. and Watanabe, N. Genetic diversity of the low-level vancomycin resistance gene vanC-2/vanC-3 and identification of a novel vanC subtype (vanC-4) in Enterococcus casseliflavus. Microb. Drug Resist. 15 (2009) 1–9. [DOI] [PMID: 19216682] |
|
[EC 6.3.2.35 created 2010] |
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|
EC |
6.3.2.36 |
Accepted name: |
4-phosphopantoate—β-alanine ligase |
Reaction: |
ATP + (R)-4-phosphopantoate + β-alanine = AMP + diphosphate + (R)-4′-phosphopantothenate |
Other name(s): |
phosphopantothenate synthetase; TK1686 protein |
Systematic name: |
(R)-4-phosphopantoate:β-alanine ligase (AMP-forming) |
Comments: |
The conversion of (R)-pantoate to (R)-4′-phosphopantothenate is part of the pathway leading to biosynthesis of 4′-phosphopantetheine, an essential cofactor of coenzyme A and acyl-carrier protein. In bacteria and eukaryotes this conversion is performed by condensation with β-alanine, followed by phosphorylation (EC 6.3.2.1 [pantoate—β-alanine ligase] and EC 2.7.1.33 [pantothenate kinase], respectively). In archaea the order of these two steps is reversed, and phosphorylation precedes condensation with β-alanine. The two archaeal enzymes that catalyse this conversion are EC 2.7.1.169, pantoate kinase, and this enzyme. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Yokooji, Y., Tomita, H., Atomi, H. and Imanaka, T. Pantoate kinase and phosphopantothenate synthetase, two novel enzymes necessary for CoA biosynthesis in the Archaea. J. Biol. Chem. 284 (2009) 28137–28145. [DOI] [PMID: 19666462] |
|
[EC 6.3.2.36 created 2011] |
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EC |
6.3.2.37 |
Accepted name: |
UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—D-lysine ligase |
Reaction: |
ATP + UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamate + D-lysine = ADP + phosphate + UDP-N-acetyl-α-D-muramoyl-L-alanyl-γ-D-glutamyl-Nε-D-lysine |
Glossary: |
muramic acid = 2-amino-3-O-[(R)-1-carboxyethyl]-2-deoxy-D-glucose |
Other name(s): |
UDP-MurNAc-L-Ala-D-Glu:D-Lys ligase; D-lysine-adding enzyme |
Systematic name: |
UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamate:D-lysine γ-ligase (ADP-forming) |
Comments: |
Involved in the synthesis of cell-wall peptidoglycan. The D-lysine is attached to the peptide chain at the N6 position. The enzyme from Thermotoga maritima also performs the reaction of EC 6.3.2.7, UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—L-lysine ligase. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Boniface, A., Bouhss, A., Mengin-Lecreulx, D. and Blanot, D. The MurE synthetase from Thermotoga maritima is endowed with an unusual D-lysine adding activity. J. Biol. Chem. 281 (2006) 15680–15686. [DOI] [PMID: 16595662] |
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[EC 6.3.2.37 created 2011, modified 2015] |
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|
EC |
6.3.2.38 |
Accepted name: |
N2-citryl-N6-acetyl-N6-hydroxylysine synthase |
Reaction: |
2 ATP + citrate + N6-acetyl-N6-hydroxy-L-lysine + H2O = 2 ADP + 2 phosphate + N6-acetyl-N2-citryl-N6-hydroxy-L-lysine |
|
For diagram of aerobactin biosynthesis, click here |
Glossary: |
citryl = 3-hydroxy-3,4-dicarboxybutanoyl |
Other name(s): |
Nα-citryl-Nε-acetyl-Nε-hydroxylysine synthase; iucA (gene name) |
Systematic name: |
citrate:N6-acetyl-N6-hydroxy-L-lysine ligase (AMP-forming) |
Comments: |
Requires Mg2+. The enzyme is involved in the biosynthesis of aerobactin, a dihydroxamate siderophore. It belongs to a class of siderophore synthases known as type A nonribosomal peptide synthase-independent synthases (NIS). Type A enzymes are responsible for the formation of amide or ester bonds between polyamines or amino alcohols and a prochiral carboxyl group of citrate. The enzyme is believed to form an adenylate intermediate prior to ligation. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Gibson, F. and Magrath, D.I. The isolation and characterization of a hydroxamic acid (aerobactin) formed by Aerobacter aerogenes 62-I. Biochim. Biophys. Acta 192 (1969) 175–184. [DOI] [PMID: 4313071] |
2. |
Maurer, P.J. and Miller, M. Microbial iron chelators: total synthesis of aerobactin and its constituent amino acid, N6-acetyl-N6-hydroxylysine. J. Am. Chem. Soc. 104 (1982) 3096–3101. |
3. |
de Lorenzo, V., Bindereif, A., Paw, B.H. and Neilands, J.B. Aerobactin biosynthesis and transport genes of plasmid ColV-K30 in Escherichia coli K-12. J. Bacteriol. 165 (1986) 570–578. [DOI] [PMID: 2935523] |
4. |
Appanna, D.L., Grundy, B.J., Szczepan, E.W. and Viswanatha, T. Aerobactin synthesis in a cell-free system of Aerobacter aerogenes 62-1. Biochim. Biophys. Acta 801 (1984) 437–443. |
5. |
Challis, G.L. A widely distributed bacterial pathway for siderophore biosynthesis
independent of nonribosomal peptide synthetases. ChemBioChem 6 (2005) 601–611. [DOI] [PMID: 15719346] |
6. |
Oves-Costales, D., Kadi, N. and Challis, G.L. The long-overlooked enzymology of a nonribosomal peptide synthetase-independent pathway for virulence-conferring siderophore biosynthesis. Chem. Commun. (Camb.) (2009) 6530–6541. [PMID: 19865642] |
|
[EC 6.3.2.38 created 2012, modified 2019] |
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|
|
|
EC |
6.3.2.39 |
Accepted name: |
aerobactin synthase |
Reaction: |
ATP + N2-citryl-N6-acetyl-N6-hydroxy-L-lysine + N6-acetyl-N6-hydroxy-L-lysine = AMP + diphosphate + aerobactin |
|
For diagram of aerobactin biosynthesis, click here |
Other name(s): |
iucC (gene name) |
Systematic name: |
N2-citryl-N6-acetyl-N6-hydroxy-L-lysine:N6-acetyl-N6-hydroxy-L-lysine ligase (AMP-forming) |
Comments: |
Requires Mg2+. The enzyme is involved in the biosynthesis of aerobactin, a dihydroxamate siderophore. It belongs to a class of siderophore synthases known as type C nonribosomal peptide synthase-independent synthases (NIS). Type C enzymes are responsible for the formation of amide or ester bonds between a variety of substrates and a prochiral carboxyl group of a citrate molecule that is already linked to a different moiety at its other prochiral carboxyl group. The enzyme is believed to form an adenylate intermediate prior to ligation. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Gibson, F. and Magrath, D.I. The isolation and characterization of a hydroxamic acid (aerobactin) formed by Aerobacter aerogenes 62-I. Biochim. Biophys. Acta 192 (1969) 175–184. [DOI] [PMID: 4313071] |
2. |
Maurer, P.J. and Miller, M. Microbial iron chelators: total synthesis of aerobactin and its constituent amino acid, N6-acetyl-N6-hydroxylysine. J. Am. Chem. Soc. 104 (1982) 3096–3101. |
3. |
Appanna, D.L., Grundy, B.J., Szczepan, E.W. and Viswanatha, T. Aerobactin synthesis in a cell-free system of Aerobacter aerogenes 62-1. Biochim. Biophys. Acta 801 (1984) 437–443. |
4. |
de Lorenzo, V., Bindereif, A., Paw, B.H. and Neilands, J.B. Aerobactin biosynthesis and transport genes of plasmid ColV-K30 in Escherichia coli K-12. J. Bacteriol. 165 (1986) 570–578. [DOI] [PMID: 2935523] |
5. |
de Lorenzo, V. and Neilands, J.B. Characterization of iucA and iucC genes of the aerobactin system of plasmid ColV-K30 in Escherichia coli. J. Bacteriol. 167 (1986) 350–355. [DOI] [PMID: 3087960] |
6. |
Challis, G.L. A widely distributed bacterial pathway for siderophore biosynthesis
independent of nonribosomal peptide synthetases. ChemBioChem 6 (2005) 601–611. [DOI] [PMID: 15719346] |
7. |
Oves-Costales, D., Kadi, N. and Challis, G.L. The long-overlooked enzymology of a nonribosomal peptide synthetase-independent pathway for virulence-conferring siderophore biosynthesis. Chem. Commun. (Camb.) (2009) 6530–6541. [PMID: 19865642] |
|
[EC 6.3.2.39 created 2012, modified 2019] |
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|
EC |
6.3.2.40 |
Accepted name: |
cyclopeptine synthase |
Reaction: |
2 ATP + S-adenosyl-L-methionine + anthranilate + L-phenylalanine = cyclopeptine + 2 AMP + 2 diphosphate + S-adenosyl-L-homocysteine |
|
For diagram of cyclopeptine, cyclopenine and viridicatin biosynthesis, click here |
Glossary: |
cyclopeptine = (3S)-3-benzyl-4-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione
4′-methoxycyclopeptine = (3S)-3-(4-methoxybenzyl)-4-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione |
Systematic name: |
S-adenosyl-L-methionine:anthranilate:L-phenylalanine ligase (cyclopeptine-forming) |
Comments: |
Cyclopeptine synthase is the key enzyme of benzodiazepine alkaloid biosynthesis in several fungi species. The enzyme is a non-ribosomal peptide synthase. It is also active with O-methyl-L-tyrosine forming 4′-methoxycyclopeptine. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Lerbs, W. and Luckner, M. Cyclopeptine synthetase activity in surface cultures of Penicillium cyclopium. J. Basic Microbiol. 25 (1985) 387–391. [DOI] [PMID: 2995633] |
2. |
Gerlach, M, Schwelle, N., Lerbs, W. and Luckner, M. Enzymatic synthesis of cyclopeptine intermediates in Penicillium cyclopium. Phytochemistry 24 (1985) 1935–1939. |
3. |
Ishikawa, N., Tanaka, H., Koyama, F., Noguchi, H., Wang, C.C., Hotta, K. and Watanabe, K. Non-heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems to form the 6,6-quinolone core of viridicatin-type fungal alkaloids. Angew. Chem. Int. Ed. Engl. 53 (2014) 12880–12884. [DOI] [PMID: 25251934] |
|
[EC 6.3.2.40 created 2013] |
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|
|
|
EC |
6.3.2.41 |
Accepted name: |
N-acetylaspartylglutamate synthase |
Reaction: |
ATP + N-acetyl-L-aspartate + L-glutamate = ADP + phosphate + N-acetyl-L-aspartyl-L-glutamate |
Other name(s): |
N-acetylaspartylglutamate synthetase; NAAG synthetase; NAAGS; RIMKLA (gene name) (ambiguous); RIMKLB (gene name) (ambiguous) |
Systematic name: |
N-acetyl-L-aspartate:L-glutamate ligase (ADP, N-acetyl-L-aspartyl-L-glutamate-forming) |
Comments: |
The enzyme, found in animals, produces the neurotransmitter N-acetyl-L-aspartyl-L-glutamate. One isoform also has the activity of EC 6.3.1.17, β-citrylglutamate synthase [2], while another isoform has the activity of EC 6.3.2.42, N-acetylaspartylglutamylglutamate synthase [3]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Becker, I., Lodder, J., Gieselmann, V. and Eckhardt, M. Molecular characterization of N-acetylaspartylglutamate synthetase. J. Biol. Chem. 285 (2010) 29156–29164. [DOI] [PMID: 20643647] |
2. |
Collard, F., Stroobant, V., Lamosa, P., Kapanda, C.N., Lambert, D.M., Muccioli, G.G., Poupaert, J.H., Opperdoes, F. and Van Schaftingen, E. Molecular identification of N-acetylaspartylglutamate synthase and β-citrylglutamate synthase. J. Biol. Chem. 285 (2010) 29826–29833. [DOI] [PMID: 20657015] |
3. |
Lodder-Gadaczek, J., Becker, I., Gieselmann, V., Wang-Eckhardt, L. and Eckhardt, M. N-acetylaspartylglutamate synthetase II synthesizes N-acetylaspartylglutamylglutamate. J. Biol. Chem. 286 (2011) 16693–16706. [DOI] [PMID: 21454531] |
|
[EC 6.3.2.41 created 2014] |
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|
EC |
6.3.2.42 |
Accepted name: |
N-acetylaspartylglutamylglutamate synthase |
Reaction: |
2 ATP + N-acetyl-L-aspartate + 2 L-glutamate = 2 ADP + 2 phosphate + N-acetyl-L-aspartyl-L-glutamyl-L-glutamate |
Other name(s): |
N-acetylaspartylglutamylglutamate synthetase; NAAG(2) synthase; NAAG synthetase II; NAAGS-II; RIMKLA (gene name) (ambiguous) |
Systematic name: |
N-acetyl-L-aspartate:L-glutamate ligase (ADP, N-acetyl-L-aspartyl-L-glutamyl-L-glutamate-forming) |
Comments: |
The enzyme, found in mammals, also has the activity of EC 6.3.2.41, N-acetylaspartylglutamate synthase. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Lodder-Gadaczek, J., Becker, I., Gieselmann, V., Wang-Eckhardt, L. and Eckhardt, M. N-acetylaspartylglutamate synthetase II synthesizes N-acetylaspartylglutamylglutamate. J. Biol. Chem. 286 (2011) 16693–16706. [DOI] [PMID: 21454531] |
|
[EC 6.3.2.42 created 2014] |
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|
EC |
6.3.2.43 |
Accepted name: |
[amino-group carrier protein]—L-2-aminoadipate ligase |
Reaction: |
ATP + an [amino-group carrier protein]-C-terminal-L-glutamate + L-2-aminoadipate = ADP + phosphate + an [amino-group carrier protein]-C-terminal-[N-(1,4-dicarboxybutyl)-L-glutamine] |
Other name(s): |
α-aminoadipate-lysW ligase; lysX (gene name); LysX (ambiguous); AAA—LysW ligase; [lysine-biosynthesis-protein LysW]-C-terminal-L-glutamate:L-2-aminoadipate ligase (ADP-forming); [lysine-biosynthesis-protein LysW]—L-2-aminoadipate ligase |
Systematic name: |
[amino-group carrier protein]-C-terminal-L-glutamate:L-2-aminoadipate ligase (ADP-forming) |
Comments: |
The enzymes from the thermophilic bacterium Thermus thermophilus and the thermophilic archaea Sulfolobus acidocaldarius and Sulfolobus tokodaii protect the amino group of L-2-aminoadipate by conjugation to the carrier protein LysW. This reaction is part of the lysine biosynthesis pathway in these organisms. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Vassylyeva, M.N., Sakai, H., Matsuura, T., Sekine, S., Nishiyama, M., Terada, T., Shirouzu, M., Kuramitsu, S., Vassylyev, D.G. and Yokoyama, S. Cloning, expression, purification, crystallization and initial crystallographic analysis of the lysine-biosynthesis LysX protein from Thermus thermophilus HB8. Acta Crystallogr. D Biol. Crystallogr. 59 (2003) 1651–1652. [PMID: 12925802] |
2. |
Horie, A., Tomita, T., Saiki, A., Kono, H., Taka, H., Mineki, R., Fujimura, T., Nishiyama, C., Kuzuyama, T. and Nishiyama, M. Discovery of proteinaceous N-modification in lysine biosynthesis of Thermus thermophilus. Nat. Chem. Biol. 5 (2009) 673–679. [DOI] [PMID: 19620981] |
3. |
Ouchi, T., Tomita, T., Horie, A., Yoshida, A., Takahashi, K., Nishida, H., Lassak, K., Taka, H., Mineki, R., Fujimura, T., Kosono, S., Nishiyama, C., Masui, R., Kuramitsu, S., Albers, S.V., Kuzuyama, T. and Nishiyama, M. Lysine and arginine biosyntheses mediated by a common carrier protein in Sulfolobus. Nat. Chem. Biol. 9 (2013) 277–283. [DOI] [PMID: 23434852] |
|
[EC 6.3.2.43 created 2014, modified 2019] |
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|
EC |
6.3.2.44 |
Accepted name: |
pantoate—β-alanine ligase (ADP-forming) |
Reaction: |
ATP + (R)-pantoate + β-alanine = ADP + phosphate + (R)-pantothenate |
|
For diagram of coenzyme A biosynthesis (early stages), click here |
Glossary: |
(R)-pantoate = (2R)-2,4-dihydroxy-3,3-dimethylbutanoate
(R)-pantothenate = 3-[(2R)-2,4-dihydroxy-3,3-dimethylbutanamido]propanoate |
Other name(s): |
pantothenate synthetase (ambiguous); pantoate—β-alanine ligase (ambiguous) |
Systematic name: |
(R)-pantoate:β-alanine ligase (ADP-forming) |
Comments: |
The enzyme, characterized from the archaeon Methanosarcina mazei, is involved in the biosynthesis of pantothenate. It is different from EC 6.3.2.1, the AMP-forming pantoate-β-alanine ligase found in bacteria and eukaryota. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Ronconi, S., Jonczyk, R. and Genschel, U. A novel isoform of pantothenate synthetase in the Archaea. FEBS J. 275 (2008) 2754–2764. [DOI] [PMID: 18422645] |
|
[EC 6.3.2.44 created 2014] |
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|
EC |
6.3.2.45 |
Accepted name: |
UDP-N-acetylmuramate—L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate ligase |
Reaction: |
ATP + UDP-N-acetyl-α-D-muramate + L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate = ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate |
Glossary: |
meso-2,6-diaminoheptanedioate = meso-2,6-diaminopimelate |
Other name(s): |
murein peptide ligase; Mpl; yjfG (gene name); UDP-MurNAc:L-Ala-γ-D-Glu-meso-A2pm ligase; UDP-N-acetylmuramate:L-alanyl-γ-D-glutamyl-meso-diaminopimelate ligase |
Systematic name: |
UDP-N-acetylmuramate:L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate ligase2015 |
Comments: |
The enzyme catalyses the reincorporation into peptidoglycan of the tripeptide L-alanyl-γ-D-glutamyl-2,6-meso-diaminoheptanedioate released during the maturation and constant remodeling of this bacterial cell wall polymer that occur during cell growth and division. The enzyme can also use the tetrapeptide L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioyl-D-alanine or the pentapeptide L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioyl-D-alanyl-D-alanine in vivo and in vitro. Requires Mg2+. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Mengin-Lecreulx, D., van Heijenoort, J. and Park, J.T. Identification of the mpl gene encoding UDP-N-acetylmuramate: L-alanyl-γ-D-glutamyl-meso-diaminopimelate ligase in Escherichia coli and its role in recycling of cell wall peptidoglycan. J. Bacteriol. 178 (1996) 5347–5352. [DOI] [PMID: 8808921] |
2. |
Herve, M., Boniface, A., Gobec, S., Blanot, D. and Mengin-Lecreulx, D. Biochemical characterization and physiological properties of Escherichia coli UDP-N-acetylmuramate:L-alanyl-γ-D-glutamyl-meso-diaminopimelate ligase. J. Bacteriol. 189 (2007) 3987–3995. [DOI] [PMID: 17384195] |
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[EC 6.3.2.45 created 2014] |
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EC |
6.3.2.46 |
Accepted name: |
fumarate—(S)-2,3-diaminopropanoate ligase |
Reaction: |
ATP + fumarate + L-2,3-diaminopropanoate = AMP + diphosphate + N3-fumaroyl-L-2,3-diaminopropanoate |
Glossary: |
N3-fumaroyl-L-2,3-diaminopropanoate = (2E)-4-{[(2S)-2-amino-2-carboxyethyl]amino}-4-oxobut-2-enoate
L-2,3-diaminopropanoate = (S)-2,3-diaminopropanoate |
Other name(s): |
DdaG; fumarate:(S)-2,3-diaminopropanoate ligase (AMP-forming) |
Systematic name: |
fumarate:L-2,3-diaminopropanoate ligase (AMP-forming) |
Comments: |
The enzyme, characterized from the bacterium Enterobacter agglomerans, is involved in biosynthesis of dapdiamide tripeptide antibiotics, a family of fumaramoyl- and epoxysuccinamoyl-peptides named for the presence of an L-2,3-diaminopropanoate (DAP) moiety and two amide linkages in their scaffold. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Hollenhorst, M.A., Clardy, J. and Walsh, C.T. The ATP-dependent amide ligases DdaG and DdaF assemble the fumaramoyl-dipeptide scaffold of the dapdiamide antibiotics. Biochemistry 48 (2009) 10467–10472. [DOI] [PMID: 19807062] |
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[EC 6.3.2.46 created 2015] |
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EC |
6.3.2.47 |
Accepted name: |
dapdiamide synthase |
Reaction: |
(1) ATP + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanine + L-valine = ADP + phosphate + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-valine (2) ATP + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanine + L-isoleucine = ADP + phosphate + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-isoleucine (3) ATP + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanine + L-leucine = ADP + phosphate + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-leucine (4) ATP + 3-({[(2R,3R)-3-carbamoyloxiran-2-yl]carbonyl}amino)-L-alanine + L-valine = ADP + phosphate + 3-({[(2R,3R)-3-carbamoyloxiran-2-yl]carbonyl}amino)-L-alanyl-L-valine |
Glossary: |
dapdiamide A = 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-valine
dapdiamide B = 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-isoleucine
dapdiamide C = 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-leucine |
Other name(s): |
DdaF; dapdiamide A synthase |
Systematic name: |
3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanine:L-valine ligase (ADP-forming) |
Comments: |
The enzyme, characterized from the bacterium Pantoea agglomerans, is involved in biosynthesis of dapdiamide tripeptide antibiotics, a family of fumaramoyl- and epoxysuccinamoyl-peptides named for the presence of an (S)-2,3-diaminopropanoate (DAP) moiety and two amide linkages in their scaffold. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Hollenhorst, M.A., Clardy, J. and Walsh, C.T. The ATP-dependent amide ligases DdaG and DdaF assemble the fumaramoyl-dipeptide scaffold of the dapdiamide antibiotics. Biochemistry 48 (2009) 10467–10472. [DOI] [PMID: 19807062] |
2. |
Hollenhorst, M.A., Bumpus, S.B., Matthews, M.L., Bollinger, J.M., Jr., Kelleher, N.L. and Walsh, C.T. The nonribosomal peptide synthetase enzyme DdaD tethers N(β)-fumaramoyl-L-2,3-diaminopropionate for Fe(II)/α-ketoglutarate-dependent epoxidation by DdaC during dapdiamide antibiotic biosynthesis. J. Am. Chem. Soc. 132 (2010) 15773–15781. [DOI] [PMID: 20945916] |
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[EC 6.3.2.47 created 2015, modified 2016] |
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EC |
6.3.2.48 |
Accepted name: |
L-arginine-specific L-amino acid ligase |
Reaction: |
ATP + L-arginine + an L-amino acid = ADP + phosphate + an L-arginyl-L-amino acid
|
Other name(s): |
RizA; L-amino acid ligase RizA |
Systematic name: |
L-arginine:L-amino acid ligase (ADP-forming) |
Comments: |
The enzyme, characterized from the bacterium Bacillus subtilis, requires Mn2+ for activity. It shows strict substrate specificity toward L-arginine as the first (N-terminal) amino acid of the product. The second amino acid could be any standard protein-building amino acid except for L-proline. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Kino, K., Kotanaka, Y., Arai, T. and Yagasaki, M. A novel L-amino acid ligase from Bacillus subtilis NBRC3134, a microorganism producing peptide-antibiotic rhizocticin. Biosci. Biotechnol. Biochem. 73 (2009) 901–907. [DOI] [PMID: 19352016] |
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[EC 6.3.2.48 created 2015] |
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|
EC |
6.3.2.49 |
Accepted name: |
L-alanine—L-anticapsin ligase |
Reaction: |
ATP + L-alanine + L-anticapsin = ADP + phosphate + bacilysin |
|
For diagram of bacilysin biosynthesis, click here |
Glossary: |
L-anticapsin = 3-[(1R,2S,6R)-5-oxo-7-oxabicyclo[4.1.0]hept-2-yl]-L-alanine
bacilysin = L-alanyl-3-[(1R,2S,6R)-5-oxo-7-oxabicyclo[4.1.0]hept-2-yl]-L-alanine |
Other name(s): |
BacD; alanine-anticapsin ligase; L-Ala-L-anticapsin ligase; ywfE (gene name) |
Systematic name: |
L-alanine:L-anticapsin ligase (ADP-forming) |
Comments: |
The enzyme, characterized from the bacterium Bacillus subtilis, is involved in the biosynthesis of the nonribosomally synthesized dipeptide antibiotic bacilysin, composed of L-alanine and L-anticapsin. The enzyme requires Mg2+ or Mn2+ for activity, and has a broad substrate specificity in vitro [1]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Tabata, K., Ikeda, H. and Hashimoto, S. ywfE in Bacillus subtilis codes for a novel enzyme, L-amino acid ligase. J. Bacteriol. 187 (2005) 5195–5202. [DOI] [PMID: 16030213] |
2. |
Tsuda, T., Suzuki, T. and Kojima, S. Crystallization and preliminary X-ray diffraction analysis of Bacillus subtilis YwfE, an L-amino-acid ligase. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 68 (2012) 203–206. [DOI] [PMID: 22298000] |
3. |
Shomura, Y., Hinokuchi, E., Ikeda, H., Senoo, A., Takahashi, Y., Saito, J., Komori, H., Shibata, N., Yonetani, Y. and Higuchi, Y. Structural and enzymatic characterization of BacD, an L-amino acid dipeptide ligase from Bacillus subtilis. Protein Sci. 21 (2012) 707–716. [DOI] [PMID: 22407814] |
4. |
Parker, J.B. and Walsh, C.T. Action and timing of BacC and BacD in the late stages of biosynthesis of the dipeptide antibiotic bacilysin. Biochemistry 52 (2013) 889–901. [DOI] [PMID: 23317005] |
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[EC 6.3.2.49 created 2006 as EC 6.3.2.28, transferred 2015 to EC 6.3.2.49] |
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|
EC |
6.3.2.50 |
Accepted name: |
tenuazonic acid synthetase |
Reaction: |
ATP + L-isoleucine + acetoacetyl-CoA = AMP + diphosphate + tenuazonic acid + CoA |
Glossary: |
tenuazonic acid = (5S)-3-acetyl-5-[(2S)-butan-2-yl]-4-hydroxy-1,5-dihydro-2H-pyrrol-2-one |
Other name(s): |
TAS1 (gene name) |
Systematic name: |
L-isoleucine:acetoacetyl-CoA ligase (tenuazonic acid-forming) |
Comments: |
This fungal enzyme, isolated from Magnaporthe oryzae, is an non-ribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) hybrid protein that consists of condensation (C), adenylation (A) and peptidyl-carrier protein (PCP) domains in the NRPS portion and a ketosynthase (KS) domain in the PKS portion. ATP is required for activation of isoleucine, which is then condensed with acetoacetyl-CoA. Cyclization and release from the enzyme are catalysed by the KS domain. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Yun, C.S., Motoyama, T. and Osada, H. Biosynthesis of the mycotoxin tenuazonic acid by a fungal NRPS-PKS hybrid enzyme. Nat. Commun. 6:8758 (2015). [DOI] [PMID: 26503170] |
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[EC 6.3.2.50 created 2017] |
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EC |
6.3.2.51 |
Accepted name: |
phosphopantothenate—cysteine ligase (ATP) |
Reaction: |
ATP + (R)-4′-phosphopantothenate + L-cysteine = AMP + diphosphate + N-[(R)-4′-phosphopantothenoyl]-L-cysteine |
|
For diagram of the late stages of CoA biosynthesis, click here |
Other name(s): |
phosphopantothenoylcysteine synthetase (ambiguous); PPCS (gene name) |
Systematic name: |
(R)-4′-phosphopantothenate:L-cysteine ligase (ATP-utilizing) |
Comments: |
A key enzyme in the production of coenzyme A. The eukaryotic enzyme requires ATP, in contrast to the bacterial enzyme, EC 6.3.2.5, phosphopantothenate—cysteine ligase, which requires CTP. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9023-50-1 |
References: |
1. |
Daugherty, M. Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. J. Biol. Chem. 277 (2002) 21431–21439. [DOI] [PMID: 11923312] |
2. |
Manoj, N., Strauss, E., Begley, T.P. and Ealick, S.E. Structure of human phosphopantothenoylcysteine synthetase at 2.3 Å Resolution. Structure 11 (2003) 927–936. [DOI] [PMID: 12906824] |
3. |
Kupke, T., Hernandez-Acosta, P. and Culianez-Macia, F.A. 4′-phosphopantetheine and coenzyme A biosynthesis in plants. J. Biol. Chem. 278 (2003) 38229–38237. [DOI] [PMID: 12860978] |
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[EC 6.3.2.51 created 2017] |
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EC |
6.3.2.52 |
Accepted name: |
jasmonoyl—L-amino acid ligase |
Reaction: |
ATP + jasmonate + an L-amino acid = AMP + diphosphate + a jasmonoyl-L-amino acid |
Other name(s): |
JAR1 (gene name); JAR4 (gene name); JAR6 (gene name); jasmonoyl—L-amino acid synthetase |
Systematic name: |
jasmonate:L-amino acid ligase |
Comments: |
Two jasmonoyl-L-amino acid synthetases have been described from Nicotiana attenuata [3] and one from Arabidopsis thaliana [1]. The N. attenuata enzymes generate jasmonoyl-L-isoleucine, jasmonoyl-L-leucine, and jasmonoyl-L-valine. The enzyme from A. thaliana could catalyse the addition of many different amino acids to jasmonate in vitro [1,4,5]. While the abundant form of jasmonate in plants is (–)-jasmonate, the active form of jasmonoyl-L-isoleucine is (+)-7-iso-jasmonoyl-L-isoleucine. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Staswick, P.E. and Tiryaki, I. The oxylipin signal jasmonic acid is activated by an enzyme that conjugates it to isoleucine in Arabidopsis. Plant Cell 16 (2004) 2117–2127. [DOI] [PMID: 15258265] |
2. |
Kang, J.H., Wang, L., Giri, A. and Baldwin, I.T. Silencing threonine deaminase and JAR4 in Nicotiana attenuata impairs jasmonic acid-isoleucine-mediated defenses against Manduca sexta. Plant Cell 18 (2006) 3303–3320. [DOI] [PMID: 17085687] |
3. |
Wang, L., Halitschke, R., Kang, J.H., Berg, A., Harnisch, F. and Baldwin, I.T. Independently silencing two JAR family members impairs levels of trypsin proteinase inhibitors but not nicotine. Planta 226 (2007) 159–167. [DOI] [PMID: 17273867] |
4. |
Guranowski, A., Miersch, O., Staswick, P.E., Suza, W. and Wasternack, C. Substrate specificity and products of side-reactions catalyzed by jasmonate:amino acid synthetase (JAR1). FEBS Lett. 581 (2007) 815–820. [DOI] [PMID: 17291501] |
5. |
Suza, W.P. and Staswick, P.E. The role of JAR1 in jasmonoyl-L-isoleucine production during Arabidopsis wound response. Planta 227 (2008) 1221–1232. [DOI] [PMID: 18247047] |
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[EC 6.3.2.52 created 2018, modified 2019] |
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EC |
6.3.2.53 |
Accepted name: |
UDP-N-acetylmuramoyl-L-alanine—L-glutamate ligase |
Reaction: |
ATP + UDP-N-acetyl-α-D-muramoyl-L-alanine + L-glutamate = ADP + phosphate + UDP-N-acetyl-α-D-muramoyl-L-alanyl-L-glutamate |
Other name(s): |
murD2 (gene name); UDP-N-acetyl-α-D-muramoyl-L-alanyl-L-glutamate synthetase; UDP-MurNAc-L-Ala-L-Glu synthetase |
Systematic name: |
UDP-N-acetylmuramoyl-L-alanine—L-glutamate ligase (ADP-forming) |
Comments: |
The enzyme, characterized from the bacterium Xanthomonas oryzae, catalyses the ligation of a terminal L-glutamate to UDP-N-acetyl-α-D-muramoyl-L-alanine. The combined activity of this enzyme and EC 5.1.1.23, UDP-N-acetyl-α-D-muramoyl-L-alanyl-L-glutamate epimerase, provides an alternative route for incorporating D-glutamate into peptidoglycan, replacing the more common combination of EC 5.1.1.3, glutamate racemase, and EC 6.3.2.9, UDP-N-acetylmuramoyl-L-alanine—D-glutamate ligase. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Feng, R., Satoh, Y., Ogasawara, Y., Yoshimura, T. and Dairi, T. A glycopeptidyl-glutamate epimerase for bacterial peptidoglycan biosynthesis. J. Am. Chem. Soc. 139 (2017) 4243–4245. [PMID: 28294606] |
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[EC 6.3.2.53 created 2018] |
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EC |
6.3.2.54 |
Accepted name: |
L-2,3-diaminopropanoate—citrate ligase |
Reaction: |
ATP + L-2,3-diaminopropanoate + citrate = AMP + diphosphate + 2-[(L-alanin-3-ylcarbamoyl)methyl]-2-hydroxybutanedioate |
Glossary: |
staphyloferrin B = 5-[(2-{[(3S)-5-{[(2S)-2-amino-2-carboxyethyl]amino}-3-carboxy-3-hydroxy-5-oxopentanoyl]amino}ethyl)amino]-2,5-dioxopentanoate |
Other name(s): |
sbnE (gene name); 2-[(L-alanin-3-ylcarbamoyl)methyl]-2-hydroxybutanedioate synthtase |
Systematic name: |
L-2,3-diaminopropanoate:citrate ligase (2-[(L-alanin-3-ylcarbamoyl)methyl]-2-hydroxybutanedioate-forming) |
Comments: |
Requires Mg2+. The enzyme, characterized from the bacterium Staphylococcus aureus, is involved in the biosynthesis of the siderophore staphyloferrin B. It belongs to a class of siderophore synthases known as type A nonribosomal peptide synthase-independent synthases (NIS). Type A NIS enzymes are responsible for the formation of amide or ester bonds between polyamines or amino alcohols and a prochiral carboxyl group of citrate. The enzyme forms a citrate adenylate intermediate prior to ligation. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Dale, S.E., Doherty-Kirby, A., Lajoie, G. and Heinrichs, D.E. Role of siderophore biosynthesis in virulence of Staphylococcus aureus: identification and characterization of genes involved in production of a siderophore. Infect. Immun. 72 (2004) 29–37. [PMID: 14688077] |
2. |
Cheung, J., Beasley, F.C., Liu, S., Lajoie, G.A. and Heinrichs, D.E. Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus. Mol. Microbiol. 74 (2009) 594–608. [PMID: 19775248] |
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[EC 6.3.2.54 created 2019] |
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EC |
6.3.2.55 |
Accepted name: |
2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate synthase |
Reaction: |
ATP + 2-[(2-aminoethylcarbamoyl)methyl]-2-hydroxybutanedioate + L-2,3-diaminopropanoate = AMP + diphosphate + 2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate |
Glossary: |
staphyloferrin B = 5-[(2-{[(3S)-5-{[(2S)-2-amino-2-carboxyethyl]amino}-3-carboxy-3-hydroxy-5-oxopentanoyl]amino}ethyl)amino]-2,5-dioxopentanoate |
Other name(s): |
sbnF (gene name) |
Systematic name: |
2-[(2-aminoethylcarbamoyl)methyl]-2-hydroxybutanedioate:L-2,3-diaminopropanoate ligase {2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate-forming} |
Comments: |
Requires Mg2+. The enzyme, characterized from the bacterium Staphylococcus aureus, is involved in the biosynthesis of the siderophore staphyloferrin B. It belongs to a class of siderophore synthases known as type C nonribosomal peptide synthase-independent synthases (NIS). Type C NIS enzymes recognize esterified or amidated derivatives of carboxylic acids. The enzyme likely forms a 2-[(2-aminoethylcarbamoyl)methyl]-2-hydroxybutanedioate adenylate intermediate prior to ligation. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Cheung, J., Beasley, F.C., Liu, S., Lajoie, G.A. and Heinrichs, D.E. Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus. Mol. Microbiol. 74 (2009) 594–608. [PMID: 19775248] |
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[EC 6.3.2.55 created 2019] |
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EC |
6.3.2.56 |
Accepted name: |
staphyloferrin B synthase |
Reaction: |
ATP + 2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate + 2-oxoglutarate = AMP + diphosphate + staphyloferrin B |
Glossary: |
staphyloferrin B = 5-[(2-{[(3S)-5-{[(2S)-2-amino-2-carboxyethyl]amino}-3-carboxy-3-hydroxy-5-oxopentanoyl]amino}ethyl)amino]-2,5-dioxopentanoate |
Other name(s): |
sbnC (gene name) |
Systematic name: |
2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate:2-oxoglutarate ligase (staphyloferrin B-forming) |
Comments: |
Requires Mg2+. The enzyme, characterized from the bacterium Staphylococcus aureus, catalyses the last step in the biosynthesis of the siderophore staphyloferrin B. It belongs to a class of siderophore synthases known as type B nonribosomal peptide synthase-independent synthases (NIS). Type B NIS enzymes recognize the δ-acid group of 2-oxoglutarate. The enzyme forms a 2-oxoglutarate adenylate intermediate prior to ligation. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Cheung, J., Beasley, F.C., Liu, S., Lajoie, G.A. and Heinrichs, D.E. Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus. Mol. Microbiol. 74 (2009) 594–608. [PMID: 19775248] |
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[EC 6.3.2.56 created 2019] |
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EC |
6.3.2.57 |
Accepted name: |
staphyloferrin A synthase |
Reaction: |
ATP + N5-[(S)-citryl]-D-ornithine + citrate = AMP + diphosphate + staphyloferrin A |
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For diagram of staphyloferrin A biosynthesis, click here |
Glossary: |
staphyloferrin A = N2-[(R)-citryl],N5-[(S)-citryl]-D-ornithine
citryl = 3-hydroxy-3,4-dicarboxybutanoyl |
Other name(s): |
sfnaB (gene name) |
Systematic name: |
N5-[(S)-citryl]-D-ornithine:citrate ligase (staphyloferrin A-forming) |
Comments: |
Requires Mg2+. The enzyme, characterized from the bacterium Staphylococcus aureus, catalyses the last step in the biosynthesis of the siderophore staphyloferrin A. It belongs to a class of siderophore synthases known as type A nonribosomal peptide synthase-independent synthases (NIS). Type A NIS enzymes are responsible for the formation of amide or ester bonds between polyamines or amino alcohols and a prochiral carboxyl group of citrate. The enzyme forms a citrate adenylate intermediate prior to ligation. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Cotton, J.L., Tao, J. and Balibar, C.J. Identification and characterization of the Staphylococcus aureus gene cluster coding for staphyloferrin A. Biochemistry 48 (2009) 1025–1035. [PMID: 19138128] |
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[EC 6.3.2.57 created 2019] |
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EC |
6.3.2.58 |
Accepted name: |
D-ornithine—citrate ligase |
Reaction: |
ATP + D-ornithine + citrate = AMP + diphosphate + N5-[(S)-citryl]-D-ornithine |
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For diagram of staphyloferrin A biosynthesis, click here |
Glossary: |
staphyloferrin A = N2-[(R)-citryl],N5-[(S)-citryl]-D-ornithine |
Other name(s): |
sfnaD (gene name) |
Systematic name: |
D-ornithine:citrate ligase {3-[(2-aminopentan-5-oylcarbamoyl)methyl]-3-hydroxybutanoate-forming} |
Comments: |
Requires Mg2+. The enzyme, characterized from the bacterium Staphylococcus aureus, is involved in the biosynthesis of the siderophore staphyloferrin A. It belongs to a class of siderophore synthases known as type A nonribosomal peptide synthase-independent synthases (NIS). Type A NIS enzymes are responsible for the formation of amide or ester bonds between polyamines or amino alcohols and a prochiral carboxyl group of citrate. The enzyme forms a citrate adenylate intermediate prior to ligation. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Cotton, J.L., Tao, J. and Balibar, C.J. Identification and characterization of the Staphylococcus aureus gene cluster coding for staphyloferrin A. Biochemistry 48 (2009) 1025–1035. [PMID: 19138128] |
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[EC 6.3.2.58 created 2019] |
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EC |
6.3.2.59 |
Accepted name: |
3-methyl-D-ornithine—L-lysine ligase |
Reaction: |
ATP + (3R)-3-methyl-D-ornithine + L-lysine = ADP + phosphate + N6-[(3R)-3-methyl-D-ornithinyl]-L-lysine |
Glossary: |
L-pyrrolysine = N6-{[(2R,3R)-3-methyl-3,4-dihydro-2H-pyrrol-2-yl]carbonyl}-L-lysine |
Other name(s): |
N6-[(2R,3R)-3-methylornithyl]-L-lysine synthase; 3-methylornithine—L-lysine ligase; pylC (gene name) |
Systematic name: |
(3R)-3-methyl-D-ornithine:L-lysine γ-ligase (ADP-forming) |
Comments: |
The enzyme participates in the biosynthesis of L-pyrrolysine, a naturally occurring, genetically coded amino acid found in some methanogenic archaea and a few bacterial species. L-pyrrolysine is present in several methyltransferases that are involved in methyl transfer from methylated amine compounds to coenzyme M. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Gaston, M.A., Zhang, L., Green-Church, K.B. and Krzycki, J.A. The complete biosynthesis of the genetically encoded amino acid pyrrolysine from lysine. Nature 471 (2011) 647–650. [DOI] [PMID: 21455182] |
2. |
Cellitti, S.E., Ou, W., Chiu, H.P., Grunewald, J., Jones, D.H., Hao, X., Fan, Q., Quinn, L.L., Ng, K., Anfora, A.T., Lesley, S.A., Uno, T., Brock, A. and Geierstanger, B.H. D-Ornithine coopts pyrrolysine biosynthesis to make and insert pyrroline-carboxy-lysine. Nat. Chem. Biol. 7 (2011) 528–530. [DOI] [PMID: 21525873] |
3. |
Quitterer, F., List, A., Beck, P., Bacher, A. and Groll, M. Biosynthesis of the 22nd genetically encoded amino acid pyrrolysine: structure and reaction mechanism of PylC at 1.5A resolution. J. Mol. Biol. 424 (2012) 270–282. [DOI] [PMID: 22985965] |
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[EC 6.3.2.59 created 2021] |
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EC |
6.3.2.60 |
Accepted name: |
glutamate—[amino group carrier protein] ligase |
Reaction: |
ATP + L-glutamate + an [amino-group carrier protein]-C-terminal-L-glutamate = ADP + phosphate + an [amino-group carrier protein]-C-terminal-γ-(L-glutamyl)-L-glutamate |
Other name(s): |
argX (gene name) |
Systematic name: |
L-glutamate:an [amino-group carrier protein]-C-terminal-L-glutamate ligase (ADP-forming) |
Comments: |
The enzyme, originally characterized from the archaeon Sulfolobus acidocaldarius, is involved in L-arginine biosynthesis. The enzyme from the archaeon Thermococcus kodakarensis is bifunctional and also catalyses the activity of EC 6.3.2.43, [amino-group carrier protein]—L-2-aminoadipate ligase. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Ouchi, T., Tomita, T., Horie, A., Yoshida, A., Takahashi, K., Nishida, H., Lassak, K., Taka, H., Mineki, R., Fujimura, T., Kosono, S., Nishiyama, C., Masui, R., Kuramitsu, S., Albers, S.V., Kuzuyama, T. and Nishiyama, M. Lysine and arginine biosyntheses mediated by a common carrier protein in Sulfolobus. Nat. Chem. Biol. 9 (2013) 277–283. [DOI] [PMID: 23434852] |
2. |
Yoshida, A., Tomita, T., Atomi, H., Kuzuyama, T. and Nishiyama, M. Lysine biosynthesis of Thermococcus kodakarensis with the capacity to function as an ornithine biosynthetic system. J. Biol. Chem. 291 (2016) 21630–21643. [DOI] [PMID: 27566549] |
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[EC 6.3.2.60 created 2021] |
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EC |
6.3.2.61 |
Accepted name: |
tubulin-glutamate ligase |
Reaction: |
n ATP + [tubulin]-L-glutamate + n L-glutamate = [tubulin]-(γ-(poly-α-L-glutamyl)-L-glutamyl)-L-glutamate + n ADP + n phosphate (overall reaction) (1a) ATP + [tubulin]-L-glutamate + L-glutamate = [tubulin]-(γ-L-glutamyl)-L-glutamate + ADP + phosphate (1b) ATP + [tubulin]-(γ-L-glutamyl)-L-glutamate + L-glutamate = [tubulin]-(α-L-glutamyl-γ-L-glutamyl)-L-glutamate + ADP + phosphate (1c) ATP + [tubulin]-(α-L-glutamyl-γ-L-glutamyl)-L-glutamate + n L-glutamate = [tubulin]-(γ-(poly-α-L-glutamyl)-L-glutamyl)-L-glutamate + n ADP + n phosphate |
Other name(s): |
α-tubulin-glutamate ligase; tubulin polyglutamylase; TTLL1 (ambiguous); TTLL5 (ambiguous); TTLL6 (ambiguous) |
Systematic name: |
[tubulin]-L-glutamate:L-glutamate ligase (ADP-forming) |
Comments: |
The eukaryotic tubulin proteins, which polymerize into microtubules, are highly modified by the addition of side-chains. The polyglutamylation reaction catalysed by this group of enzymes consists of two biochemically distinct steps: initiation and elongation. Initiation comprises the formation of an isopeptide bond with the γ-carboxyl group of the glutamate acceptor site in a glutamate-rich C-terminal region of tubulin, whereas elongation consists of the addition of glutamate residues linked by regular peptide bonds to the γ-linked residue. This entry describes enzymes that act on both α- and β-tubulins. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Regnard, C., Audebert, S., Desbruyeres, Denoulet, P. and Edde, B. Tubulin polyglutamylase: partial purification and enzymatic properties. Biochemistry 37 (1998) 8395–8404. [DOI] [PMID: 9622491] |
2. |
Regnard, C., Desbruyeres, E., Denoulet, P. and Edde, B. Tubulin polyglutamylase: isozymic variants and regulation during the cell cycle in HeLa cells. J. Cell Sci. 112 (1999) 4281–4289. [DOI] [PMID: 10564646] |
3. |
Westermann, S., Plessmann, U. and Weber, K. Synthetic peptides identify the minimal substrate requirements of tubulin polyglutamylase in side chain elongation. FEBS Lett. 459 (1999) 90–94. [DOI] [PMID: 10508923] |
4. |
Janke, C., Rogowski, K., Wloga, D., Regnard, C., Kajava, A.V., Strub, J.M., Temurak, N., van Dijk, J., Boucher, D., van Dorsselaer, A., Suryavanshi, S., Gaertig, J. and Edde, B. Tubulin polyglutamylase enzymes are members of the TTL domain protein family. Science 308 (2005) 1758–1762. [DOI] [PMID: 15890843] |
5. |
van Dijk, J., Rogowski, K., Miro, J., Lacroix, B., Edde, B. and Janke, C. A targeted multienzyme mechanism for selective microtubule polyglutamylation. Mol. Cell 26 (2007) 437–448. [DOI] [PMID: 17499049] |
6. |
Wloga, D., Rogowski, K., Sharma, N., Van Dijk, J., Janke, C., Edde, B., Bre, M.H., Levilliers, N., Redeker, V., Duan, J., Gorovsky, M.A., Jerka-Dziadosz, M. and Gaertig, J. Glutamylation on α-tubulin is not essential but affects the assembly and functions of a subset of microtubules in Tetrahymena thermophila. Eukaryot Cell 7 (2008) 1362–1372. [DOI] [PMID: 18586949] |
7. |
van Dijk, J., Miro, J., Strub, J.M., Lacroix, B., van Dorsselaer, A., Edde, B. and Janke, C. Polyglutamylation is a post-translational modification with a broad range of substrates. J. Biol. Chem. 283 (2008) 3915–3922. [DOI] [PMID: 18045879] |
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[EC 6.3.2.61 created 2021] |
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EC |
6.3.2.62 |
Accepted name: |
β-tubulin-glutamate ligase |
Reaction: |
n ATP + [β-tubulin]-L-glutamate + n L-glutamate = [β-tubulin]-(γ-(poly-α-L-glutamyl)-L-glutamyl)-L-glutamate + n ADP + n phosphate (overall reaction) (1a) ATP + [β-tubulin]-L-glutamate + L-glutamate = [β-tubulin]-(γ-L-glutamyl)-L-glutamate + ADP + phosphate (1b) ATP + [β-tubulin]-(γ-L-glutamyl)-L-glutamate + L-glutamate = [β-tubulin]-(α-L-glutamyl-γ-L-glutamyl)-L-glutamate + ADP + phosphate (1c) ATP + [β-tubulin]-(α-L-glutamyl-γ-L-glutamyl)-L-glutamate + n L-glutamate = [β-tubulin]-(γ-(poly-α-L-glutamyl)-L-glutamyl)-L-glutamate + n ADP + n phosphate |
Other name(s): |
β-tubulin polyglutamylase; TTLL4 (ambiguous); TTLL7 (ambiguous) |
Systematic name: |
[β-tubulin]-L-glutamate:L-glutamate ligase (ADP-forming) |
Comments: |
The eukaryotic tubulin proteins, which polymerize into microtubules, are highly modified by the addition of side-chains. The polyglutamylation reaction catalysed by this group of enzymes consists of two biochemically distinct steps: initiation and elongation. Initiation comprises the formation of an isopeptide bond with the γ-carboxyl group of the glutamate acceptor site, whereas elongation consists of the addition of glutamate residues linked by regular peptide bonds to the γ-linked residue. This entry describes enzymes that act on β-tubulins and other proteins with glutamate-rich regions but not on α-tubulins. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Regnard, C., Audebert, S., Desbruyeres, Denoulet, P. and Edde, B. Tubulin polyglutamylase: partial purification and enzymatic properties. Biochemistry 37 (1998) 8395–8404. [DOI] [PMID: 9622491] |
2. |
Regnard, C., Desbruyeres, E., Denoulet, P. and Edde, B. Tubulin polyglutamylase: isozymic variants and regulation during the cell cycle in HeLa cells. J. Cell Sci. 112 (1999) 4281–4289. [DOI] [PMID: 10564646] |
3. |
Ikegami, K., Mukai, M., Tsuchida, J., Heier, R.L., Macgregor, G.R. and Setou, M. TTLL7 is a mammalian β-tubulin polyglutamylase required for growth of MAP2-positive neurites. J. Biol. Chem. 281 (2006) 30707–30716. [DOI] [PMID: 16901895] |
4. |
van Dijk, J., Miro, J., Strub, J.M., Lacroix, B., van Dorsselaer, A., Edde, B. and Janke, C. Polyglutamylation is a post-translational modification with a broad range of substrates. J. Biol. Chem. 283 (2008) 3915–3922. [DOI] [PMID: 18045879] |
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[EC 6.3.2.62 created 2021] |
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EC |
6.3.2.63 |
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 |
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. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
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. [DOI] [PMID: 18630910] |
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[EC 6.3.2.63 created 2024] |
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EC |
6.3.2.64 |
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. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
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. [DOI] [PMID: 18956041] |
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[EC 6.3.2.64 created 2024] |
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EC |
6.3.3.1 |
Accepted name: |
phosphoribosylformylglycinamidine cyclo-ligase |
Reaction: |
ATP + 2-(formamido)-N1-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole |
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For diagram of the early stages of purine biosynthesis, click here |
Other name(s): |
phosphoribosylaminoimidazole synthetase; AIR synthetase; 5′-aminoimidazole ribonucleotide synthetase; 2-(formamido)-1-N-(5-phosphoribosyl)acetamidine cyclo-ligase (ADP-forming) |
Systematic name: |
2-(formamido)-N1-(5-phosphoribosyl)acetamidine cyclo-ligase (ADP-forming) |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9023-53-4 |
References: |
1. |
Levenberg, B. and Buchanan, J.M. Properties of the purines. XII. Structure, enzymatic synthesis, and metabolism of 5-aminoimidazole ribotide. J. Biol. Chem. 224 (1957) 1005–1018. [PMID: 13405929] |
2. |
Levenberg, B. and Buchanan, J.M. Biosynthesis of the purines. XIII. Structure, enzymatic synthesis, and metabolism of (α-N-formyl)-glycinamidine ribotide. J. Biol. Chem. 224 (1957) 1018–1027. [PMID: 13405930] |
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[EC 6.3.3.1 created 1961, modified 2000] |
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EC |
6.3.3.2 |
Accepted name: |
5-formyltetrahydrofolate cyclo-ligase |
Reaction: |
ATP + 5-formyltetrahydrofolate = ADP + phosphate + 5,10-methenyltetrahydrofolate |
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For diagram of folate cofactors, click here and for diagram of C1 metabolism, click here |
Other name(s): |
5,10-methenyltetrahydrofolate synthetase; formyltetrahydrofolic cyclodehydrase; 5-formyltetrahydrofolate cyclodehydrase |
Systematic name: |
5-formyltetrahydrofolate cyclo-ligase (ADP-forming) |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37318-64-2 |
References: |
1. |
Greenberg, D.M., Wynston, L.K. and Nagabhushanan, A. Further studies on N5-formyltetrahydrofolic acid cyclodehydrase. Biochemistry 4 (1965) 1872–1878. |
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[EC 6.3.3.2 created 1972] |
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EC |
6.3.3.3 |
Accepted name: |
dethiobiotin synthase |
Reaction: |
ATP + 7,8-diaminononanoate + CO2 = ADP + phosphate + dethiobiotin |
Other name(s): |
desthiobiotin synthase |
Systematic name: |
7,8-diaminononanoate:carbon-dioxide cyclo-ligase (ADP-forming) |
Comments: |
CTP has half the activity of ATP. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37259-75-9 |
References: |
1. |
Krell, K. and Eisenberg, M.A. The purification and properties of dethiobiotin synthetase. J. Biol. Chem. 245 (1970) 6558–6566. [PMID: 4921568] |
2. |
Yang, H.-C., Tani, Y. and Ogata, K. Synthesis of biotin vitamers from biotin diaminocarboxylic acid or 7,8-diaminopelargonic acid by a purified enzyme of Pseudomonas graveolens. Agric. Biol. Chem. 34 (1970) 1748–1750. |
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[EC 6.3.3.3 created 1976] |
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EC |
6.3.3.4 |
Accepted name: |
(carboxyethyl)arginine β-lactam-synthase |
Reaction: |
ATP + L-N2-(2-carboxyethyl)arginine = AMP + diphosphate + deoxyamidinoproclavaminate |
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For diagram of clavulanate biosynthesis, click here |
Other name(s): |
L-2-N-(2-carboxyethyl)arginine cyclo-ligase (AMP-forming) |
Systematic name: |
L-N2-(2-carboxyethyl)arginine cyclo-ligase (AMP-forming) |
Comments: |
Forms part of the pathway for the biosythesis of the β-lactamase inhibitor clavulanate in Streptomyces clavuligerus. It has been proposed [3] that L-N2-(2-carboxyethyl)arginine is first converted into an acyl-AMP by reaction with ATP and loss of diphosphate, and that the β-lactam ring is then formed by the intramolecular attack of the β-nitrogen on the activated carboxy group. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Zhou, J., Kelly, W.L., Bachmann, B.O., Gunsior, M., Townsend, C.A. and Solomon, E.I. Spectroscopic studies of substrate interactions with clavaminate synthase 2, a multifunctional α-KG-dependent non-heme iron enzyme: Correlation with mechanisms and reactivities. J. Am. Chem. Soc. 123 (2001) 7388–7398. [DOI] [PMID: 11472170] |
2. |
Townsend, C.A. New reactions in clavulanic acid biosynthesis. Curr. Opin. Chem. Biol. 6 (2002) 583–589. [DOI] [PMID: 12413541] |
3. |
Bachmann, B.O., Li, R. and Townsend, C.A. β-Lactam synthetase: a new biosynthetic enzyme. Proc. Natl. Acad. Sci. USA 95 (1998) 9082–9086. [DOI] [PMID: 9689037] |
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[EC 6.3.3.4 created 2003] |
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EC |
6.3.3.5 |
Accepted name: |
O-ureido-D-serine cyclo-ligase |
Reaction: |
O-ureido-D-serine + ATP + H2O = D-cycloserine + CO2 + NH3 + ADP + phosphate |
Glossary: |
O-ureido-D-serine = (2R)-2-amino-3-[(carbamoylamino)oxy]propanoate |
Other name(s): |
dcsG (gene name) |
Systematic name: |
O-ureido-D-serine cyclo-ligase (D-cycloserine-forming) |
Comments: |
The enzyme participates in the biosynthetic pathway of D-cycloserine, an antibiotic substance produced by several Streptomyces species. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Kumagai, T., Koyama, Y., Oda, K., Noda, M., Matoba, Y. and Sugiyama, M. Molecular cloning and heterologous expression of a biosynthetic gene cluster for the antitubercular agent D-cycloserine produced by Streptomyces lavendulae. Antimicrob. Agents Chemother. 54 (2010) 1132–1139. [DOI] [PMID: 20086163] |
2. |
Uda, N., Matoba, Y., Kumagai, T., Oda, K., Noda, M. and Sugiyama, M. Establishment of an in vitro D-cycloserine-synthesizing system by using O-ureido-L-serine synthase and D-cycloserine synthetase found in the biosynthetic pathway. Antimicrob. Agents Chemother. 57 (2013) 2603–2612. [DOI] [PMID: 23529730] |
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[EC 6.3.3.5 created 2013] |
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