Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1980 Feb 15;186(2):613–616. doi: 10.1042/bj1860613

The conversion of cephalosporins to 7 alpha-methoxycephalosporins by cell-free extracts of Streptomyces clavuligerus.

J O'Sullivan, E P Abraham
PMCID: PMC1161616  PMID: 7378068

Abstract

In the presence of S-adenosylmethionine, 2-oxoglutarate, Fe2+ and a reducing agent, cell-free extracts of Streptomyces clavuligerus convert cephalosporin C and O-carbamoyldeacetylcephalosporin C into 7 alpha-methoxy derivatives. No synthesis of a 7 alpha-methoxy derivative of deacetylcephalosporin C was detected in the system used, and the 7 alpha-methoxy derivative of deacetoxycephalosporin C was produced only in relatively small amounts. It appears that the 7 alpha-methoxy group is introduced after the cephalosporin ring system has been formed and that its introduction may represent the final step in a biosynthetic pathway.

Full text

PDF
614

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  2. Brewer S. J., Boyle T. T., Turner M. K. The carbamoylation of the 3-hydroxymethyl group of 7alpha-methoxy-7beta-(5-D-aminoadipamido)-3-hydroxymethylceph-3-em-4-carboxylic acid (desacetyl-7alpha-methoxycephalosporin C) by homogenates of Streptomyces clavuligerus [proceedings]. Biochem Soc Trans. 1977;5(4):1026–1029. doi: 10.1042/bst0051026. [DOI] [PubMed] [Google Scholar]
  3. JEFFERY J. D., ABRAHAM E. P., NEWTON G. G. Deacetylcephalosporin C. Biochem J. 1961 Dec;81:591–596. doi: 10.1042/bj0810591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Laskey R. A., Mills A. D. Quantitative film detection of 3H and 14C in polyacrylamide gels by fluorography. Eur J Biochem. 1975 Aug 15;56(2):335–341. doi: 10.1111/j.1432-1033.1975.tb02238.x. [DOI] [PubMed] [Google Scholar]
  5. Nagarajan R., Boeck L. D., Gorman M., Hamill R. L., Higgens C. E., Hoehn M. M., Stark W. M., Whitney J. G. Beta-lactam antibiotics from Streptomyces. J Am Chem Soc. 1971 May 5;93(9):2308–2310. doi: 10.1021/ja00738a035. [DOI] [PubMed] [Google Scholar]
  6. O'Sullivan J., Aplin R. T., Stevens C. M., Abraham E. P. Biosynthesis of a 7-alpha-methoxycephalosporin. Incorporation of molecular oxygen. Biochem J. 1979 Apr 1;179(1):47–52. doi: 10.1042/bj1790047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. O'Sullivan J., Bleaney R. C., Huddleston J. A., Abraham E. P. Incorporation of 3H from delta-(L-alpha-amino (4,5-3H)adipyl)-L-cysteinyl-D-(4,4-3H)valine into isopenicillin N. Biochem J. 1979 Nov 15;184(2):421–426. doi: 10.1042/bj1840421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Smith B., Warren S. C., Newton G. G., Abraham E. P. Biosynthesis of penicillin N and cephalosporin C. Antibiotic production and other features of the metabolism of Cephalosporium sp. Biochem J. 1967 Jun;103(3):877–890. doi: 10.1042/bj1030877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Stapley E. O., Jackson M., Hernandez S., Zimmerman S. B., Currie S. A., Mochales S., Mata J. M., Woodruff H. B., Hendlin D. Cephamycins, a new family of beta-lactam antibiotics. I. Production by actinomycetes, including Streptomyces lactamdurans sp. n. Antimicrob Agents Chemother. 1972 Sep;2(3):122–131. doi: 10.1128/aac.2.3.122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Turner M. K., Farthing J. E., Brewer S. J. The oxygenation of [3-methyl-3H]desacetoxycephalosporin C [7beta-(5-D-aminadipamido)-3-methylceph-3-em-4-carboxylic acid] to [3-hydroxymethyl-3H]desacetylcephalosporin C by 2-oxoglutarate-linked dioxygenases from Acremonium chrysogenum and Streptomyces clavuligerus. Biochem J. 1978 Sep 1;173(3):839–850. doi: 10.1042/bj1730839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Whitney J. G., Brannon D. R., Mabe J. A., Wicker K. J. Incorporation of labeled precursors into A16886B, a novel -lactam antibiotic produced by Streptomyces clavuligerus. Antimicrob Agents Chemother. 1972 Mar;1(3):247–251. doi: 10.1128/aac.1.3.247. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES