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. 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.

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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]

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