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. 1968 Mar;95(3):952–958. doi: 10.1128/jb.95.3.952-958.1968

Effect of Structural and Stereochemical Methylproline Isomers on Actinomycin Biosynthesis

Tadashi Yoshida 1,2,1, Anthony Mauger 1,2, Herbert Weissbach 1,2, Edward Katz 1,2
PMCID: PMC252115  PMID: 4171116

Abstract

The inhibitory effect of methylprolines on actinomycin biosynthesis by Streptomyces antibioticus was studied; the order of effectiveness was 3- >4- >5-methyl-dl-proline. Cis-3-methyl-dl-proline was 14 times more active than the trans isomer. It was also found that 4- and, possibly, 5-methylproline were incorporated into the actinomycin molecule. When 4-methylproline was present, three new actinomycins, representing 50 to 60% of the antibiotic mixture, were synthesized. Growth of the organism may be stimulated at concentrations (0.1 to 1.0 μg per ml) of 3-methylproline that inhibit antibiotic formation, thus providing additional evidence for a different mechanism of actinomycin synthesis from that of protein synthesis. Azetidine-2-carboxylic acid, piperdine-2-carboxylic acid, and hydroxyproline (but not sarcosine) reversed the inhibition due to 3-methylproline.

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Selected References

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

  1. BERG T. L., FROHOLM L. O., LALAND S. G. THE BIOSYNTHESIS OF GRAMICIDIN S IN A CELL-FREE SYSTEM. Biochem J. 1965 Jul;96:43–52. doi: 10.1042/bj0960043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Borowska Z. K., Tatum E. L. Biosynthesis of edeine by Bacillus brevis Vm4 in vivo and in vitro. Biochim Biophys Acta. 1966 Jan 18;114(1):206–209. doi: 10.1016/0005-2787(66)90273-5. [DOI] [PubMed] [Google Scholar]
  3. CERUTTI P., IKEDA K., WITKOP B. THE SELECTIVE PHOTOREDUCTION OF URIDINE IN POLYNUCLEOTIDES. J Am Chem Soc. 1965 Jun 5;87:2505–2507. doi: 10.1021/ja01089a045. [DOI] [PubMed] [Google Scholar]
  4. CORNELL N., SNOKE J. E. BIOSYNTHESIS OF BACITRACIN AND PROTEIN. Biochim Biophys Acta. 1964 Nov 15;91:533–536. doi: 10.1016/0926-6550(64)90086-6. [DOI] [PubMed] [Google Scholar]
  5. Fowden L., Lewis D., Tristram H. Toxic amino acids: their action as antimetabolites. Adv Enzymol Relat Areas Mol Biol. 1967;29:89–163. doi: 10.1002/9780470122747.ch3. [DOI] [PubMed] [Google Scholar]
  6. KATZ E. Biogenesis of the actinomycins. Ann N Y Acad Sci. 1960 Oct 5;89:304–322. doi: 10.1111/j.1749-6632.1960.tb20154.x. [DOI] [PubMed] [Google Scholar]
  7. KATZ E., GOSS W. A. Controlled biosynthesis of actinomycin with sarcosine. Biochem J. 1959 Nov;73:458–465. doi: 10.1042/bj0730458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. KATZ E., GOSS W. A. Influence of amino-acids of actinomycin biosynthesis. Nature. 1958 Dec 13;182(4650):1668–1669. doi: 10.1038/1821668b0. [DOI] [PubMed] [Google Scholar]
  9. KATZ E., PIENTA P., SIVAK A. The role of nutrition in the synthesis of actinomycin. Appl Microbiol. 1958 Jul;6(4):236–241. doi: 10.1128/am.6.4.236-241.1958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. KATZ E., WEISSBACH H. Effect of chloromycetin and penicillin on the incorporation of amino acids into actinomycin and protein by Streptomyces antibioticus. Biochem Biophys Res Commun. 1962 Jul 3;8:186–190. doi: 10.1016/0006-291x(62)90260-7. [DOI] [PubMed] [Google Scholar]
  11. KATZ E., WEISSBACH H. Incorporation of C14-labeled amino acids into actinomycin and protein by Streptomyces antibioticus. J Biol Chem. 1963 Feb;238:666–675. [PubMed] [Google Scholar]
  12. KATZ E., WISE M., WEISSBACH H. ACTINOMYCIN BIOSYNTHESIS. DIFFERENTIAL EFFECT OF CHLORAMPHENICOL ON PROTEIN AND PEPTIDE ANTIBIOTIC SYNTHESIS. J Biol Chem. 1965 Jul;240:3071–3078. [PubMed] [Google Scholar]
  13. MITOMA C., SMITH T. E., FRIEDBERG F., RAYFORD C. R. Incorporation of hydroxyproline into tissue proteins by chick embryos. J Biol Chem. 1959 Jan;234(1):78–80. [PubMed] [Google Scholar]
  14. Mach B., Reich E., Tatum E. L. SEPARATION OF THE BIOSYNTHESIS OF THE ANTIBIOTIC POLYPEPTIDE TYROCIDINE FROM PROTEIN BIOSYNTHESIS. Proc Natl Acad Sci U S A. 1963 Jul;50(1):175–181. doi: 10.1073/pnas.50.1.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nakamura S., Tanaka N., Umezawa H. Bottromycin A1, A2 and their structures. J Antibiot (Tokyo) 1966 Jan;19(1):10–12. [PubMed] [Google Scholar]
  16. Nishimura J. S., Bowers W. F. Evidence for the incorporation of L-thiazolidine-4-carboxylate into actinomycins by Streptomyces antibioticus. Biochem Biophys Res Commun. 1967 Sep 7;28(5):665–670. doi: 10.1016/0006-291x(67)90366-x. [DOI] [PubMed] [Google Scholar]
  17. PAULUS H., GRAY E. THE BIOSYNTHESIS OF POLYMYXIN B BY GROWING CULTURES OF BACILLUS POLYMYXA. J Biol Chem. 1964 Mar;239:865–871. [PubMed] [Google Scholar]
  18. SIVAK A., KATZ E. Biosynthesis of the actinomycin chromophore. Influence of alpha-, 4-, 5-, and 6-methyl-DL-tryptophan on actinomycin synthesis. Biochim Biophys Acta. 1962 Jul 30;62:80–90. doi: 10.1016/0006-3002(62)90493-6. [DOI] [PubMed] [Google Scholar]
  19. SIVAK A., MELONI M. L., NOBILI F., KATZ E. Biosynthesis of the actinomycin chromophore. Studies with DL-[7alpha-14C] tryptophan and L-[Me-14C] methionine. Biochim Biophys Acta. 1962 Feb 26;57:283–289. doi: 10.1016/0006-3002(62)91121-6. [DOI] [PubMed] [Google Scholar]
  20. TROLL W., LINDSLEY J. A photometric method for the determination of proline. J Biol Chem. 1955 Aug;215(2):655–660. [PubMed] [Google Scholar]
  21. Yoshida T., Mauger A., Witkop B., Katz E. Influence of methylproline isomers upon actinomycin biosynthesis. Biochem Biophys Res Commun. 1966 Oct 5;25(1):66–72. doi: 10.1016/0006-291x(66)90641-3. [DOI] [PubMed] [Google Scholar]

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