Abstract
In Streptomyces lactamdurans, the precursor of the alpha-aminoadipoyl side-chain of cephamycin C is L-lysine. In this regard, streptomycetes differ strikingly from the fungi, which produce alpha-aminoadipic acid during the synthesis, rather than the breakdown, of L-lysine. Studies using a cell-free system showed that an aminoadipic acid. The product of this reaction was trapped and subsequently purified by ion-exchange chromatography. Thin-layer chromatography, spectrophotometry, and amino acid oxidase digestion studies identified the reaction product as L-1-piperideine-6-carboxylate, implying enzymatic removal of the epsilon amino group of L-lysine. This enzymatic activity (E.C. 2.6.1.36; L-lysine: 2-oxoglutarate 6-aminotransferase) is highly unusual and was previously conclusively demonstrated only in the genus Flavobacterium. In S. lactamdurans, the specific activity of this enzyme reaches a peak early in the fermentation (approximately 20 h) and decreases as the antibiotic begins to appear.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- ARNSTEIN H. R., ARTMAN M., MORRIS D., TOMS E. J. Sulphur-containing amino acids and peptides in the mycelium of Penicillium chrysogenum. Biochem J. 1960 Aug;76:353–357. doi: 10.1042/bj0760353. [DOI] [PMC free article] [PubMed] [Google Scholar]
- ARNSTEIN H. R., MORRIS D. The structure of a peptide, containing alpha-aminoadipic acid, cystine and valine, present in the mycelium of Penicillium chrysogenum. Biochem J. 1960 Aug;76:357–361. doi: 10.1042/bj0760357. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aharonowitz Y., Demain A. L. Carbon catabolite regulation of cephalosporin production in Streptomyces clavuligerus. Antimicrob Agents Chemother. 1978 Aug;14(2):159–164. doi: 10.1128/aac.14.2.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aharonowitz Y., Demain A. L. Nitrogen nutrition and regulation of cephalosporin production in Streptomyces clavuligerus. Can J Microbiol. 1979 Jan;25(1):61–67. doi: 10.1139/m79-010. [DOI] [PubMed] [Google Scholar]
- Calvert A. F., Rodwell V. W. Metabolism of pipecolic acid in a Pseudomonas species. 3. L-alpha-aminoadipate delta-semialdehyde:nicotinamide adenine dinucleotide oxidoreductase. J Biol Chem. 1966 Jan 25;241(2):409–414. [PubMed] [Google Scholar]
- DAVIS B. D. Biosynthetic interrelations of lysine, diaminopimelic acid, and threonine in mutants of Escherichia coli. Nature. 1952 Mar 29;169(4300):534–536. doi: 10.1038/169534a0. [DOI] [PubMed] [Google Scholar]
- DEWEY D. L., WORK E. Diaminopimelic acid decarboxylase. Nature. 1952 Mar 29;169(4300):533–534. doi: 10.1038/169533a0. [DOI] [PubMed] [Google Scholar]
- Fothergill J. C., Guest J. R. Catabolism of L-lysine by Pseudomonas aeruginosa. J Gen Microbiol. 1977 Mar;99(1):139–155. doi: 10.1099/00221287-99-1-139. [DOI] [PubMed] [Google Scholar]
- KUO M. H., SAUNDERS P., BROQUIST H. P. A metabolite of alpha-aminoadipic acid in yeast: relation to lysine biosynthesis. Biochem Biophys Res Commun. 1962 Jul 3;8:227–231. doi: 10.1016/0006-291x(62)90268-1. [DOI] [PubMed] [Google Scholar]
- Kirkpatrick J. R., Doolin L. E., Godfrey O. W. Lysine biosynthesis in Streptomyces lipmanii: implications in antibiotic biosynthesis. Antimicrob Agents Chemother. 1973 Nov;4(5):542–550. doi: 10.1128/aac.4.5.542. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Loder P. B., Abraham E. P. Isolation and nature of intracellular peptides from a cephalosporin C-producing Cephalosporium sp. Biochem J. 1971 Jul;123(3):471–476. doi: 10.1042/bj1230471. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Malik V. S., Vining L. C. Metabolism of chloramphenicol by the producing organism. Can J Microbiol. 1970 Mar;16(3):173–179. doi: 10.1139/m70-030. [DOI] [PubMed] [Google Scholar]
- Neuss N., Nash C. H., Lemke P. A., Grutzner J. B. The use of carbon-13 nuclear magnetic resonance (Cmr) spectroscopy in biosynthetic studies. Incorporation of carboxyl and methyl carbon-13 labeled acetates into cephalosporin C. J Am Chem Soc. 1971 May 5;93(9):2336–2339. doi: 10.1021/ja00738a052. [DOI] [PubMed] [Google Scholar]
- Pirt S. J., Righelato R. C. Effect of Growth Rate on the Synthesis of Penicillin by Penicillium chrysogenum in Batch and Chemostat Cultures. Appl Microbiol. 1967 Nov;15(6):1284–1290. doi: 10.1128/am.15.6.1284-1290.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SCHWEET R. S. The quantitative determination of proline and pipecolic acid with ninhydrin. J Biol Chem. 1954 Jun;208(2):603–613. [PubMed] [Google Scholar]
- 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]
- Smith R. L., Bungay H. R., Pittenger R. C. Growth-Biosynthesis Relationships in Erythromycin Fermentation. Appl Microbiol. 1962 Jul;10(4):293–296. doi: 10.1128/am.10.4.293-296.1962. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Soda K., Misono H. L-Lysine:alpha-ketoglutarate aminotransferase. II. Purification, crystallization, and properties. Biochemistry. 1968 Nov;7(11):4110–4119. doi: 10.1021/bi00851a046. [DOI] [PubMed] [Google Scholar]
- 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]
- TROWN P. W., ABRAHAM E. P., NEWTON G. G., HALE C. W., MILLER G. A. Incorporation of acetate into cephalosporin C. Biochem J. 1962 Jul;84:157–166. doi: 10.1042/bj0840157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]