Deacetoxycephalosporin-C hydroxylase
| Deacetoxycephalosporin-C hydroxylase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 1.14.11.26 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| |||||||||
Deacetoxycephalosporin-C hydroxylase (EC 1.14.11.26) is an enzyme that catalyzes the chemical reaction
The two substrates of this enzyme are deacetoxycephalosporin C and oxygen. Its product is deacetylcephalosporin C.[1][2][3][4]
This enzyme is an oxidoreductase with systematic name deacetoxycephalosporin-C,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating). Other names in common use include deacetylcephalosporin C synthase, 3'-methylcephem hydroxylase, DACS, DAOC hydroxylase, and deacetoxycephalosporin C hydroxylase.[1] This non-heme iron protein generates a ferryl group at its active site; Fe(IV)=O is the species that transfers its oxygen to the substrate.[5]
The mechanism used by these 2-oxoglutarate-dependent oxygenases requires 2-oxoglutaric acid to activate the iron oxygen complex, and this gives succinic acid and carbon dioxide when the second atom of the molecular oxygen is removed.[6]
Biological role
This enzyme is involved in the biosynthesis of cephalosporin C in Acremonium chrysogenum, which is used for the industrial production of that antibiotic.[7][8][9][10]
References
- ^ a b Enzyme 1.14,11,26 at KEGG Pathway Database.
- ^ Dotzlaf JE, Yeh WK (1987). "Copurification and characterization of deacetoxycephalosporin C synthetase/hydroxylase from Cephalosporium acremonium". J. Bacteriol. 169 (4): 1611–8. doi:10.1128/jb.169.4.1611-1618.1987. PMC 211989. PMID 3558321.
- ^ Baker BJ, Dotzlaf JE, Yeh WK (1991). "Deacetoxycephalosporin C hydroxylase of Streptomyces clavuligerus Purification, characterization, bifunctionality, and evolutionary implication". J. Biol. Chem. 266 (8): 5087–93. doi:10.1016/S0021-9258(19)67759-8. PMID 2002049.
- ^ Schofield CJ; Lipscomb, SJ; Hewitson, KS; Hensgens, CM; Baldwin, JE; Schofield, CJ (2004). "Controlling the substrate selectivity of deacetoxycephalosporin/deacetylcephalosporin C synthase". J. Biol. Chem. 279 (15): 15420–6. doi:10.1074/jbc.M313928200. PMID 14734549.
- ^ Mbenza, Naasson M.; Vadakkedath, Praveen G.; McGillivray, Duncan J.; Leung, Ivanhoe K.H. (2017). "NMR studies of the non-haem Fe(II) and 2-oxoglutarate-dependent oxygenases". Journal of Inorganic Biochemistry. 177: 384–394. doi:10.1016/j.jinorgbio.2017.08.032. PMID 28893416.
- ^ Clifton, Ian J.; Hsueh, Li-Ching; Baldwin, Jack E.; Harlos, Karl; Schofield, Christopher J. (2001). "Structure of proline 3-hydroxylase". European Journal of Biochemistry. 268 (24): 6625–6636. doi:10.1046/j.0014-2956.2001.02617.x. PMID 11737217.
- ^ AT, Kosalkova K; Gutiérrez, S; Fernández, FJ; Velasco, J; Fierro, F; Marcos, AT; Kosalkova, K (1994). "Expression of genes and processing of enzymes for the biosynthesis of penicillins and cephalosporins". Antonie van Leeuwenhoek. 65 (3): 227–43. doi:10.1007/BF00871951. PMID 7847890.
- ^ Coque JJ, Enguita FJ, Cardoza RE, Martin JF, Liras P (1996). "Characterization of the cefF gene of Nocardia lactamdurans encoding a 3'-methylcephem hydroxylase different from the 7-cephem hydroxylase". Appl. Microbiol. Biotechnol. 44 (5): 605–9. doi:10.1007/BF00172492. PMID 8703431.
- ^ Ghag SK, Brems DN, Hassell TC, Yeh WK (1996). "Refolding and purification of Cephalosporium acremonium deacetoxycephalosporin C synthetase/hydroxylase from granules of recombinant Escherichia coli". Biotechnol. Appl. Biochem. 24 (2): 109–19. doi:10.1111/j.1470-8744.1996.tb00393.x. PMID 8865604.
- ^ Liu, Ling; Chen, Zhen; Liu, Wuyi; et al. (2022). "Cephalosporin C biosynthesis and fermentation in Acremonium chrysogenum". Applied Microbiology and Biotechnology. 106 (19–20): 6413–6426. doi:10.1007/s00253-022-12181-w. PMID 36114850.