EC |
1.14.11.26 |
Accepted name: |
deacetoxycephalosporin-C hydroxylase |
Reaction: |
deacetoxycephalosporin C + 2-oxoglutarate + O2 = deacetylcephalosporin C + succinate + CO2 |
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For diagram of cephalosporin biosynthesis, click here |
Other name(s): |
deacetylcephalosporin C synthase; 3′-methylcephem hydroxylase; DACS; DAOC hydroxylase; deacetoxycephalosporin C hydroxylase |
Systematic name: |
deacetoxycephalosporin-C,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating) |
Comments: |
Requires iron(II). The enzyme can also use 3-exomethylenecephalosporin C as a substrate to form deacetoxycephalosporin C, although more slowly [2]. In Acremonium chrysogenum, the enzyme forms part of a bifunctional protein along with EC 1.14.20.1, deactoxycephalosporin-C synthase. It is a separate enzyme in Streptomyces clavuligerus. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 69772-89-0 |
References: |
1. |
Dotzlaf, J.E. and Yeh, W.K. Copurification and characterization of deacetoxycephalosporin C synthetase/hydroxylase from Cephalosporium acremonium. J. Bacteriol. 169 (1987) 1611–1618. [DOI] [PMID: 3558321] |
2. |
Baker, B.J., Dotzlaf, J.E. and Yeh, W.K. Deacetoxycephalosporin C hydroxylase of Streptomyces clavuligerus. Purification, characterization, bifunctionality, and evolutionary implication. J. Biol. Chem. 266 (1991) 5087–5093. [PMID: 2002049] |
3. |
Coque, J.J., Enguita, F.J., Cardoza, R.E., Martin, J.F. and Liras, P. Characterization of the cefF gene of Nocardia lactamdurans encoding a 3′-methylcephem hydroxylase different from the 7-cephem hydroxylase. Appl. Microbiol. Biotechnol. 44 (1996) 605–609. [PMID: 8703431] |
4. |
Ghag, S.K., Brems, D.N., Hassell, T.C. and Yeh, W.K. Refolding and purification of Cephalosporium acremonium deacetoxycephalosporin C synthetase/hydroxylase from granules of recombinant Escherichia coli. Biotechnol. Appl. Biochem. 24 (1996) 109–119. [PMID: 8865604] |
5. |
Lloyd, M.D., Lipscomb, S.J., Hewitson, K.S., Hensgens, C.M., Baldwin, J.E. and Schofield, C.J. Controlling the substrate selectivity of deacetoxycephalosporin/deacetylcephalosporin C synthase. J. Biol. Chem. 279 (2004) 15420–15426. [DOI] [PMID: 14734549] |
6. |
Wu, X.B., Fan, K.Q., Wang, Q.H. and Yang, K.Q. C-terminus mutations of Acremonium chrysogenum deacetoxy/deacetylcephalosporin C synthase with improved activity toward penicillin analogs. FEMS Microbiol. Lett. 246 (2005) 103–110. [DOI] [PMID: 15869968] |
7. |
Martín, J.F., Gutiérrez, S., Fernández, F.J., Velasco, J., Fierro, F., Marcos, A.T. and Kosalkova, K. Expression of genes and processing of enzymes for the biosynthesis of penicillins and cephalosporins. Antonie Van Leeuwenhoek 65 (1994) 227–243. [PMID: 7847890] |
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[EC 1.14.11.26 created 2005] |
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EC |
1.14.20.1 |
Accepted name: |
deacetoxycephalosporin-C synthase |
Reaction: |
penicillin N + 2-oxoglutarate + O2 = deacetoxycephalosporin C + succinate + CO2 + H2O |
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For diagram of penicillin-N and deacetoxycephalosporin-C biosynthesis, click here |
Other name(s): |
DAOCS; penicillin N expandase; DAOC synthase |
Systematic name: |
penicillin-N,2-oxoglutarate:oxygen oxidoreductase (ring-expanding) |
Comments: |
Forms part of the penicillin biosynthesis pathway (for pathway, click here). |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 85746-10-7 |
References: |
1. |
Cantwell, C., Beckmann, R., Whiteman, P., Queener, S.W. and Abraham, E.P. Isolation of deacetoxycephalosporin-c from fermentation broths of Penicillium chrysogenum transformants - construction of a new fungal biosynthetic-pathway. Proc. R. Soc. Lond. B Biol. Sci. 248 (1992) 283–289. [DOI] [PMID: 1354366] |
2. |
Lee, H.J., Lloyd, M.D., Harlos, K., Clifton, I.J., Baldwin, J.E. and Schofield, C.J. Kinetic and crystallographic studies on deacetoxycephalosporin C synthase (DAOCS). J. Mol. Biol. 308 (2001) 937–948. [DOI] [PMID: 11352583] |
3. |
Yeh, W.K., Ghag, S.K. and Queener, S.W. Enzymes for epimerization of isopenicillin N, ring expansion of penicillin N, and 3′-hydroxylation of deacetoxycephalosporin C. Function, evolution, refolding, and enzyme engineering. Ann. N.Y. Acad. Sci. 672 (1992) 396–408. |
4. |
Valegaard, K., van Scheltinga, A.C.T., Lloyd, M.D., Hara, T., Ramaswamy, S., Perrakis, A., Thompson, A., Lee, H.-J., Baldwin, J.E., Schofield, C.J., Hajdu, J. and Andersson, I. Structure of a cephalosporin synthase. Nature 394 (1998) 805–809. [DOI] [PMID: 9723623] |
5. |
Dotzlaf, J.E. and Yeh, W.K. Purification and properties of deacetoxycephalosporin C synthase from
recombinant Escherichia coli and its comparison with the native enzyme
purified from Streptomyces clavuligerus. J. Biol. Chem. 264 (1989) 10219–10227. [PMID: 2656705] |
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[EC 1.14.20.1 created 2002] |
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EC |
2.3.1.175 |
Accepted name: |
deacetylcephalosporin-C acetyltransferase |
Reaction: |
acetyl-CoA + deacetylcephalosporin C = CoA + cephalosporin C |
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For diagram of cephalosporin biosynthesis, click here |
Other name(s): |
acetyl-CoA:deacetylcephalosporin-C acetyltransferase; DAC acetyltransferase; cefG; deacetylcephalosporin C acetyltransferase; acetyl coenzyme A:DAC acetyltransferase; acetyl-CoA:DAC acetyltransferase; CPC acetylhydrolase; acetyl-CoA:DAC O-acetyltransferase; DAC-AT |
Systematic name: |
acetyl-CoA:deacetylcephalosporin-C O-acetyltransferase |
Comments: |
This enzyme catalyses the final step in the biosynthesis of cephalosporin C. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 57827-76-6 |
References: |
1. |
Matsuyama, K., Matsumoto, H., Matsuda, A., Sugiura, H., Komatsu, K. and Ichikawa, S. Purification of acetyl coenzyme A: deacetylacephalosporin C O-acetyltransferase from Acremonium chrysogenum. Biosci. Biotechnol. Biochem. 56 (1992) 1410–1412. [DOI] [PMID: 1368946] |
2. |
Gutiérrez, S., Velasco, J., Fernandez, F.J. and Martín, J.F. The cefG gene of Cephalosporium acremonium is linked to the cefEF gene and encodes a deacetylcephalosporin C acetyltransferase closely related to homoserine O-acetyltransferase. J. Bacteriol. 174 (1992) 3056–3064. [DOI] [PMID: 1569032] |
3. |
Matsuda, A., Sugiura, H., Matsuyama, K., Matsumoto, H., Ichikawa, S. and Komatsu, K. Cloning and disruption of the cefG gene encoding acetyl coenzyme A: deacetylcephalosporin C O-acetyltransferase from Acremonium chrysogenum. Biochem. Biophys. Res. Commun. 186 (1992) 40–46. [DOI] [PMID: 1632779] |
4. |
Gutiérrez, S., Velasco, J., Marcos, A.T., Fernández, F.J., Fierro, F., Barredo, J.L., Díez, B. and Martín, J.F. Expression of the cefG gene is limiting for cephalosporin biosynthesis in Acremonium chrysogenum. Appl. Microbiol. Biotechnol. 48 (1997) 606–614. [PMID: 9421924] |
5. |
Velasco, J., Gutierrez, S., Campoy, S. and Martin, J.F. Molecular characterization of the Acremonium chrysogenum cefG gene product: the native deacetylcephalosporin C acetyltransferase is not processed into subunits. Biochem. J. 337 (1999) 379–385. [PMID: 9895280] |
6. |
Martín, J.F., Gutiérrez, S., Fernández, F.J., Velasco, J., Fierro, F., Marcos, A.T. and Kosalkova, K. Expression of genes and processing of enzymes for the biosynthesis of penicillins and cephalosporins. Antonie Van Leeuwenhoek 65 (1994) 227–243. [PMID: 7847890] |
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[EC 2.3.1.175 created 2005] |
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EC |
2.6.1.74 |
Accepted name: |
cephalosporin-C transaminase |
Reaction: |
(7R)-7-(5-carboxy-5-oxopentanoyl)aminocephalosporinate + D-glutamate = cephalosporin C + 2-oxoglutarate |
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For diagram of cephalosporin biosynthesis, click here |
Glossary: |
cephalosporin C = (7R)-7-(5-carboxy-5-oxopentanamido)cephalosporanate |
Other name(s): |
cephalosporin C aminotransferase; L-alanine:cephalosporin-C aminotransferase |
Systematic name: |
cephalosporin-C:2-oxoglutarate aminotransferase |
Comments: |
A number of D-amino acids, including D-alanine, D-aspartate and D-methionine can also act as amino-group donors. Although this enzyme acts on several free D-amino acids, it differs from EC 2.6.1.21, D-alanine transaminase, in that it can use cephalosporin C as an amino donor. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 122096-91-7 |
References: |
1. |
Aretz, W. and Sauber, K. Novel D-amino acid transaminase. Ann. N.Y. Acad. Sci. 542 (1988) 366–370. [PMID: 3228235] |
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[EC 2.6.1.74 created 1992, modified 2005] |
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EC |
3.1.1.41 |
Accepted name: |
cephalosporin-C deacetylase |
Reaction: |
cephalosporin C + H2O = deacetylcephalosporin C + acetate |
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For diagram of cephalosporin biosynthesis, click here |
Other name(s): |
cephalosporin C acetyl-hydrolase; cephalosporin C acetylase; cephalosporin acetylesterase; cephalosporin C acetylesterase; cephalosporin C acetyl-esterase; cephalosporin C deacetylase |
Systematic name: |
cephalosporin-C acetylhydrolase |
Comments: |
Hydrolyses the acetyl ester bond on the 10-position of the antibiotic cephalosporin C. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 52227-71-1 |
References: |
1. |
Fujisawa, Y., Shirafuji, H., Kida, M. and Nara, K. New findings on cephalosporin C biosynthesis. Nat. New Biol. 246 (1973) 154–155. [PMID: 4519146] |
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[EC 3.1.1.41 created 1976] |
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EC |
3.5.1.93 |
Accepted name: |
glutaryl-7-aminocephalosporanic-acid acylase |
Reaction: |
(7R)-7-(4-carboxybutanamido)cephalosporanate + H2O = (7R)-7-aminocephalosporanate + glutarate |
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For diagram of cephalosporin biosynthesis, click here |
Other name(s): |
7β-(4-carboxybutanamido)cephalosporanic acid acylase; cephalosporin C acylase; glutaryl-7-ACA acylase; CA; GCA; GA; cephalosporin acylase; glutaryl-7-aminocephalosporanic acid acylase; GL-7-ACA acylase |
Systematic name: |
(7R)-7-(4-carboxybutanamido)cephalosporanate amidohydrolase |
Comments: |
Forms 7-aminocephalosporanic acid, a key intermediate in the synthesis of cephem antibiotics. It reacts only weakly with cephalosporin C. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 56645-46-6 |
References: |
1. |
Ishii, Y., Saito, Y., Fujimura, T., Sasaki, H., Noguchi, Y., Yamada, H., Niwa, M. and Shimomura, K. High-level production, chemical modification and site-directed mutagenesis of a cephalosporin C acylase from Pseudomonas strain N176. Eur. J. Biochem. 230 (1995) 773–778. [DOI] [PMID: 7607251] |
2. |
Kinoshita, T., Tada, T., Saito, Y., Ishii, Y., Sato, A. and Murata, M. Crystallization and preliminary X-ray analysis of cephalosporin C acylase from Pseudomonas sp. strain N176. Acta Crystallogr. D Biol. Crystallogr. 56 (2000) 458–459. [PMID: 10739919] |
3. |
Monti, D., Carrea, G., Riva, S., Baldaro, E. and Frare, G. Characterization of an industrial biocatalyst: immobilized glutaryl-7-ACA acylase. Biotechnol. Bioeng. 70 (2000) 239–244. [PMID: 10972935] |
4. |
Kwon, T.H., Rhee, S., Lee, Y.S., Park, S.S. and Kim, K.H. Crystallization and preliminary X-Ray diffraction analysis of
glutaryl-7-aminocephalosporanic acid acylase from Pseudomonas sp. GK16. J. Struct. Biol. 131 (2000) 79–81. [DOI] [PMID: 10945972] |
5. |
Kim, Y., Yoon, K.-H., Khang, Y., Turley, S. and Hol, W.G.J. The 2.0 Å crystal structure of cephalosporin acylase. Structure 8 (2000) 1059–1068. [DOI] [PMID: 11080627] |
6. |
Huang, X., Zeng, R., Ding, X., Mao, X., Ding, Y., Rao, Z., Xie, Y., Jiang, W. and Zhao, G. Affinity alkylation of the Trp-B4 residue of the β-subunit of the glutaryl 7-aminocephalosporanic acid acylase of Pseudomonas sp. 130. J. Biol. Chem. 277 (2002) 10256–10264. [DOI] [PMID: 11782466] |
7. |
Kim, J.K., Yang, I.S., Rhee, S., Dauter, Z., Lee, Y.S., Park, S.S. and Kim, K.H. Crystal structures of glutaryl 7-aminocephalosporanic acid acylase: insight into autoproteolytic activation. Biochemistry 42 (2003) 4084–4093. [DOI] [PMID: 12680762] |
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[EC 3.5.1.93 created 2005] |
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EC |
5.1.1.17 |
Accepted name: |
isopenicillin-N epimerase |
Reaction: |
isopenicillin N = penicillin N |
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For diagram of penicillin-N and deacetoxycephalosporin-C biosynthesis, click here |
Systematic name: |
penicillin-N 5-amino-5-carboxypentanoyl-epimerase |
Comments: |
This enzyme contains pyridoxal phosphate. Epimerization at C-5 of the 5-amino-5-carboxypentanoyl group to form penicillin N is required to make a substrate for EC 1.14.20.1, deactoxycephalosporin-C synthase, to produce cephalosporins. Forms part of the penicillin biosynthesis pathway (for pathway, click here). |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 88201-43-8 |
References: |
1. |
Usui, S. and Yu, C.-A. Purification and properties of isopenicillin-N epimerase from Streptomyces clavuligerus. Biochim. Biophys. Acta 999 (1989) 78–85. [DOI] [PMID: 2804141] |
2. |
Laiz, L., Liras, P., Castro, J.M. and Martín, J.F. Purification and characterization of the isopenicillin-N epimerase from Nocardia lactamdurans. J. Gen. Microbiol. 136 (1990) 663–671. |
3. |
Cantwell, C., Beckmann, R., Whiteman, P., Queener, S.W. and Abraham, E.P. Isolation of deacetoxycephalosporin-c from fermentation broths of Penicillium chrysogenum transformants - construction of a new fungal biosynthetic-pathway. Proc. R. Soc. Lond. B Biol. Sci. 248 (1992) 283–289. [DOI] [PMID: 1354366] |
4. |
Yeh, W.K., Ghag, S.K. and Queener, S.W. Enzymes for epimerization of isopenicillin N, ring expansion of penicillin N, and 3′-hydroxylation of deacetoxycephalosporin C. Function, evolution, refolding, and enzyme engineering. Ann. N.Y. Acad. Sci. 672 (1992) 396–408. |
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[EC 5.1.1.17 created 2002] |
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