Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1969 Aug;63(4):1335–1342. doi: 10.1073/pnas.63.4.1335

PEPTIDYL TRANSFERS IN GRAMICIDIN S BIOSYNTHESIS FROM ENZYME-BOUND THIOESTER INTERMEDIATES*

Wieland Gevers 1,†, Horst Kleinkauf 1,‡, Fritz Lipmann 1
PMCID: PMC223469  PMID: 5260936

Abstract

The biosynthesis of the peptide antibiotic gramicidin S involves successive peptidyl transfer reactions between intermediates bound in thioester linkages to two active enzyme fractions, I and II. Fraction II activates and recemizes phenylalanine, and then initiates peptidyl transfer by catalyzing a reaction between the carboxyl group of D-phenylalanine, bound to an enzymic sulfhydryl group, and the free imino group of L-proline, one of four L-amino acids all linked by their carboxyl functions to separate sulfhydryl groups on fraction I. Successive reactions of this type in the active centers of the multienzyme complex of fraction I lead to the formation of thioester-bonded nascent peptide chains and, ultimately, of the antibiotic product.

Full text

PDF
1339

Selected References

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

  1. BRODIE J. D., WASSON G., PORTER J. W. ENZYME-BOUND INTERMEDIATES IN THE BIOSYNTHESIS OF MEVALONIC AND PALMITIC AICDS. J Biol Chem. 1964 May;239:1346–1356. [PubMed] [Google Scholar]
  2. Bredesen J. E., Berg T. L., Figenschou K. J., Froholm L. O., Laland S. G. Purification of the gramicidin S synthesizing activity in Bacillus brevis extracts. Eur J Biochem. 1968 Aug;5(3):433–436. doi: 10.1111/j.1432-1033.1968.tb00388.x. [DOI] [PubMed] [Google Scholar]
  3. Dalziel Keith. A kinetic interpretation of the allosteric model of Monod, Wyman, and Changeux. FEBS Lett. 1968 Oct;1(5):339–342. doi: 10.1016/0014-5793(68)80150-4. [DOI] [PubMed] [Google Scholar]
  4. Gevers W., Kleinkauf H., Lipmann F. The activation of amino acids for biosynthesis of gramicidin S. Proc Natl Acad Sci U S A. 1968 May;60(1):269–276. doi: 10.1073/pnas.60.1.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Heinrich C. P., Fruton J. S. The action of dipeptidyl transferase as a polymerase. Biochemistry. 1968 Oct;7(10):3556–3565. doi: 10.1021/bi00850a033. [DOI] [PubMed] [Google Scholar]
  6. KEARNEY E. B., SINGER T. P. The L-amino acid oxidases of snake venom. IV. The effect of anions on the reversible inactivation. Arch Biochem Biophys. 1951 Oct;33(3):397–413. doi: 10.1016/0003-9861(51)90126-9. [DOI] [PubMed] [Google Scholar]
  7. Kleinkauf H., Gevers W., Lipmann F. Interrelation between activation and polymerization in gramicidin S biosynthesis. Proc Natl Acad Sci U S A. 1969 Jan;62(1):226–233. doi: 10.1073/pnas.62.1.226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. OVERATH P., KELLERMAN G. M., LYNEN F., FRITZ H. P., KELLER H. J. [On the mechanism of the rearrangement of methylmalonyl-Co A into succinyl-Co A. II. Experiments on the mechanism of action of methylmalonyl-Co A isomerase and methylmalonyl-Co A racemase]. Biochem Z. 1962;335:500–518. [PubMed] [Google Scholar]
  9. Otani S., Yamanoi T., Saito Y. Ornithine activating enzyme from Bacillus brevis. Biochem Biophys Res Commun. 1968 Nov 25;33(4):620–626. doi: 10.1016/0006-291x(68)90341-0. [DOI] [PubMed] [Google Scholar]
  10. STADTMAN E. R. The purification and properties of phosphotransacetylase. J Biol Chem. 1952 May;196(2):527–534. [PubMed] [Google Scholar]
  11. Tomino S., Yamada M., Itoh H., Kurahashik Cell-free synthesis of gramicidin S. Biochemistry. 1967 Aug;6(8):2552–2560. doi: 10.1021/bi00860a037. [DOI] [PubMed] [Google Scholar]
  12. Vagelos P. R., Majerus P. W., Alberts A. W., Larrabee A. R., Ailhaud G. P. Structure and function of the acyl carrier protein. Fed Proc. 1966 Sep-Oct;25(5):1485–1494. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES