Ribosomal Effects of Thiostrepton and Related Antibiotics
Thiostrepton (alias bryamycin) is a polypeptide antibiotic of sixteen residues with several modifications to the amino acids, for example cyclizatior of cysteine residues. A portion of the molecule is cyclic and there is an ester linkage to a terminal quinaldic acid derivative (Anderson et al., 1970). Thiostrepton inhibits protein synthesis on procaryotic ribosomes by binding firmly to the 50s ribosomal subunit (Weisblum & Demohn, 1970a) with 1:1 stoichiometry (Sopori & Lengyel, 1972; Gordon & Highland, 1974) and recently (Highland et al., 1974), ribosomal protein L11 of E. coli was implicated in the thiostreptonbinding reaction. To date however, no detailed analysis of thiostreptonresistant ribosomes has been reported although a mutant of E. coli, resistant to the related antibiotic, thiopeptin, possesses altered 50s ribosomal subunits (Liou et al., 1973). Other antibiotics, chemically related to thiostrepton and thiopeptin, include siomycin and sporangiomycin, and although the complete structure is only available for thiostrepton it is already apparent that this group of compounds have identical (or closely similar) biochemical modes of action. (For a review, see Cundliffe 1972a; also Pirali et al., 1972).
KeywordsInhibit Protein Synthesis Antibiotic Production Fusidic Acid Streptomyces Griseus Nascent Peptide
Unable to display preview. Download preview PDF.
- BROOKES, P., FULLER, A.T. and J. WALKER: Chemistry of micrococcin P. P.rt 1. J. Chem. Soc. p. 689 (1957).Google Scholar
- BULOCK, J.D.: Intermediary metabolism and antibiotic synthesis. Adv. in App. Microbiol. 3, 293–342 (1961).Google Scholar
- CUNDLIFFE, E.: Antibiotic inhibitors of ribosome function, in Molecular basis of antibiotic action. Authors E.F. Gale, E. CundliffeGoogle Scholar
- P.E. Reynolds, M.H. Richmond and M.J. Waring. Pages 278–379. Wiley and Sons, London (1972a).Google Scholar
- GORDON, J. and J.H. HIGHLAND: Binding of thiostrepton to the ribosomes of E. coli Characterization and stoichiometry of binding. J. Biol. Chem. in press (1974).Google Scholar
- HIGHLAND, J.H., HOWARD, G.A., OCHSNER, E., STÖFFLER, G., HASENBANK, R. and J. GORDON: Identification of the ribosomal protein responsible for the binding of thiostrepton to E. coli ribosomes. J. Biol. Chem. in press (1974).Google Scholar
- KINOSHITA, T., LIOU, Y.-F.and N. TANAKA: Inhibition by thiopeptin of ribosomal functions associated with T and G factors. Biochem. Biophys. Research Commun. 44, 859–863 (1971).Google Scholar
- LIOU, Y.-F., KINOSHITA, T., TANAKA, N. and M. Y.SHIKAWA: Studies on the ribosomes of a thiopeptin-resistant mutant of E. coli. J. Antibiotics 26, 711–716 (1973).Google Scholar
- PIRALI, G., LANCINI, G.C., PARISI, B. and F. SALA: Interaction of sporangiomycin with the bacterial ribosome. J. Antibiotics 25, 561–568 (1972).Google Scholar
- WEISBLUM, B7-and V. DEMOHN: Thiostrepton, an inhibitor of 50s ribosome subunit function. Biochem. Biophys. Research Commun. 101, 1073–1075 (1970a).Google Scholar
- WOODRUFF, H.B.: The physiology of antibiotic production: The role of the producing organism. Symp. Soc. Gen. Microbiol. 16, 22–46 (1966).Google Scholar