Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1983 Nov;24(5):735–741. doi: 10.1128/aac.24.5.735

Effect of phosphate and amino acids on echinomycin biosynthesis by Streptomyces echinatus.

J V Formica, M J Waring
PMCID: PMC185935  PMID: 6660849

Abstract

Streptomyces echinatus produces only echinomycin (quinomycin A), in contrast to other streptomycetes, which produce families of quinoxaline antibiotics differing in the amino acid composition of the oligopeptide (quinomycins A, B, B0, C, D, and E) or the structure of the sulfur-containing cross bridge (triostins A, B, and C). Attempts were made to establish conditions for directed biosynthesis with S. echinatus. The lability of the peptide lactone to alkaline pH was obviated by using high levels of phosphate or HEPES [4-(2-hydroxyethyl)-1-piperazineethane-sulfonic acid] buffer in the production medium. Maintaining the pH below 7.5 resulted in an apparent stimulation of production. Amino acids which serve as structural components or as precursors of echinomycin were employed singly or in combination with nitrate in a chemically defined medium. Based on specific yield (micrograms of echinomycin per milligram of mycelia [dry weight]), D- and L-serine, D-alanine, L-valine, and L-phenylalanine produced equivalent yields of antibiotic which were approximately twofold greater than yields obtained with nitrate alone. In contrast, L-alanine, beta-alanine, and L-threonine produced a three- to fourfold stimulation of production. Although the other amino acids diminished antibiotic production, L-isoleucine, which ostensibly was inhibitory to production, supported the accumulation of a quinoxaline antibiotic in which the cross-bridge sulfur lacked a methyl group.

Full text

PDF
735

Selected References

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

  1. Dell A., Williams D. H., Morris H. R., Smith G. A., Feeney J., Roberts G. C. Structure revision of the antibiotic echinomycin. J Am Chem Soc. 1975 Apr 30;97(9):2497–2502. doi: 10.1021/ja00842a029. [DOI] [PubMed] [Google Scholar]
  2. Formica J. V., Apple M. A. Production, isolation, and properties of azetomycins. Antimicrob Agents Chemother. 1976 Feb;9(2):214–221. doi: 10.1128/aac.9.2.214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Formica J. V., Katz E. Isolation, purification, and characterization of pipecolic acid-containing actinomycins, Pip 2, Pip 1 , and Pip 1 . J Biol Chem. 1973 Mar 25;248(6):2066–2071. [PubMed] [Google Scholar]
  4. Fox K. R., Gauvreau D., Goodwin D. C., Waring M. J. Binding of quinoline analogues of echinomycin to deoxyribonucleic acid. Role of the chromophores. Biochem J. 1980 Dec 1;191(3):729–742. doi: 10.1042/bj1910729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Haavik H. I. Studies on the formation of bacitracin by Bacillus licheniformis: effect of inorganic phosphate. J Gen Microbiol. 1974 Sep;84(1):226–230. doi: 10.1099/00221287-84-1-226. [DOI] [PubMed] [Google Scholar]
  6. KATZ E. Influence of valine, isoleucine, and related compounds on actinomycin synthesis. J Biol Chem. 1960 Apr;235:1090–1094. [PubMed] [Google Scholar]
  7. Lee J. S., Waring M. J. Interaction between synthetic analogues of quinoxaline antibiotics and nucleic acids. Changes in mechanism and specificity related to structural alterations. Biochem J. 1978 Jul 1;173(1):129–144. doi: 10.1042/bj1730129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Martin J. F., Demain A. L. Control of antibiotic biosynthesis. Microbiol Rev. 1980 Jun;44(2):230–251. doi: 10.1128/mr.44.2.230-251.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. SHOJI J. I., TORI K., OTSUKA H. CONFIGURATION OF N,BETA-DIMETHYLLEUCINE, A CONSTITUENT AMINO ACID OF TRIOSTIN C. J Org Chem. 1965 Aug;30:2772–2776. doi: 10.1021/jo01019a064. [DOI] [PubMed] [Google Scholar]
  10. Waring M. J., Wakelin L. P. Echinomycin: a bifunctional intercalating antibiotic. Nature. 1974 Dec 20;252(5485):653–657. doi: 10.1038/252653a0. [DOI] [PubMed] [Google Scholar]
  11. Williamson M. P., Gauvreau D., Williams D. H., Waring M. J. Structure and conformation of fourteen antibiotics of the quinoxaline group determined by 1H NMR. J Antibiot (Tokyo) 1982 Jan;35(1):62–66. doi: 10.7164/antibiotics.35.62. [DOI] [PubMed] [Google Scholar]
  12. Yoshida T., Katagiri K. Influence of isoleucine upon quinomycin biosynthesis by Streptomyces sp. 732. J Bacteriol. 1967 Apr;93(4):1327–1331. doi: 10.1128/jb.93.4.1327-1331.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES