Ribosomal Effects of Thiostrepton and Related Antibiotics

  • Eric Cundliffe
  • Janet E. Beven
  • Peter D. Dixon
Conference paper
Part of the Topics in Infectious Diseases book series (TIDIS, volume 1)


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).


Inhibit Protein Synthesis Antibiotic Production Fusidic Acid Streptomyces Griseus Nascent Peptide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. ANDERSON, B., HODGKIN, D.C. and M.A. WISWAMITRA: The structure of thiostrepton. Nature 225 233–235 (1970).PubMedCrossRefGoogle Scholar
  2. BALLESTA, J.P.G. and D. VAZQUEZ: Elongation factor T-dependent hydrolysis of guanine triphosphate resistant to thiostrepton. Proc. Nat. Acad. Sci. USA 69, 3058–3062 (1972).PubMedCrossRefGoogle Scholar
  3. BENVENISTE, R. and J. DAVIES: Aminoglycoside antibiotic-inactivating enzymes in actinomycetes similar to those present in clinical isolates of antibiotic-resistant bacteria. Proc. Nat. Acad. Sci. USA 70, 2276–2280 (1973).PubMedCrossRefGoogle Scholar
  4. BODLEY, J.W., LIN, L. and J.H. HIGHLAND: Thiostrepton prevents the formation of a ribosome•G factor guanine nucleotide complex. Biochem. Biophys. Research Commun. 41, 1406–1411 (1970).CrossRefGoogle Scholar
  5. BODLEY, J.W., ZIEVE, F.J., LIN, L. and S.T. ZIEVE: Formation of the ribosome•G factor-GDP complex in the presence of fusidic acid. Biochem. Biophys. Research Commun. 37, 437–443 (1969).CrossRefGoogle Scholar
  6. BROOKES, P., FULLER, A.T. and J. WALKER: Chemistry of micrococcin P. P.rt 1. J. Chem. Soc. p. 689 (1957).Google Scholar
  7. BULOCK, J.D.: Intermediary metabolism and antibiotic synthesis. Adv. in App. Microbiol. 3, 293–342 (1961).Google Scholar
  8. BURNS, D.J.W. and E. CUNDLIFFE: Bacterial protein synthesis. A novel system for studying antibiotic action in vivo. Eur. J. Biochem. 37, 570–574 (1973).PubMedCrossRefGoogle Scholar
  9. CABRER, B., VAZQUEZ, D. and J. MODOLELL: Inhibition by elongation factor G of aminoacyl-tRNA binding to ribosomes. Proc. Nat. Acad. Sci. USA 69, 733–736 (1972).PubMedCrossRefGoogle Scholar
  10. CANNON, M. and K. BURNS: Modes of action of erythromycin and thiostrepton as inhibitors of protein synthesis. FEBS Lett. 18, 1–5 (1971).PubMedCrossRefGoogle Scholar
  11. CELMA, M.L., VAZQUEZ, D. and J. MODOLELL: Failure of fusidic acid and siomycin to block ribosomes in the pretranslocated state. Biochem. Biophys. Research Commun. 48, 1240–1246 (1972).CrossRefGoogle Scholar
  12. CUNDLIFFE, E: The mode of action of thiostrepton in vivo. Biochem. Biophys. Research Commun. 44, 912–917 (1971).CrossRefGoogle Scholar
  13. CUNDLIFFE, E.: Antibiotic inhibitors of ribosome function, in Molecular basis of antibiotic action. Authors E.F. Gale, E. CundliffeGoogle Scholar
  14. P.E. Reynolds, M.H. Richmond and M.J. Waring. Pages 278–379. Wiley and Sons, London (1972a).Google Scholar
  15. CUNDLIFFE, E.: The mode of action of fusidic acid. Biochem. Biophys. Research Commun. 46, 1974–1801 (1972b).CrossRefGoogle Scholar
  16. CUNDLIFFE, E. and K.McQUILLEN: Bacterial protein synthesis: The effects of antibiotics. J. Mol. Biol. 30, 137–146 (1967).PubMedCrossRefGoogle Scholar
  17. 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
  18. HEATLEY, N.G. and H.M. DOERY: The preparation and some properties of purified micrococcin. Biochem. J. 50, 247–253 (1951).PubMedGoogle Scholar
  19. 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
  20. HIGHLAND, J.H., LIN, L. and J.W. BODLEY: Protection of ribosomes from thiostrepton inactivation by the binding of G factor and GDP. Biochemistry 10, 4404–4409 (1971).PubMedCrossRefGoogle Scholar
  21. 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
  22. KINOSHITA, T., KUWANA, G. and N. TANAKA: Association of fusidic acid sensitivity with G factor in a protein synthesizing system. Biochem. Biophys. Research Commun. 33, 769–773 (1968).CrossRefGoogle Scholar
  23. 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
  24. MILLER, D.L.: Elongation factors EF-Tu and EF-G interact at related sites on ribosomes. Proc. Nat. Acad. Sci. USA 69, 752–755 (1972).PubMedCrossRefGoogle Scholar
  25. MODOLELL, J., CABRER, B., PARMEGGIANI, A. and D. VAZQUEZ: Inhibition by siomycin and thiostrepton of both aminoacyl-tRNA and factor G binding to ribosomes. Proc. Nat. Acad. Sci. USA 68, 1796–1800 (1971).PubMedCrossRefGoogle Scholar
  26. PESTKA, S.: Thiostrepton: A ribosomal inhibitor of translocation. Biochem. Biophys. Research Commun. 40, 667–674 (1970).CrossRefGoogle Scholar
  27. PESTKA, S. and N. BROT: Effect of antibiotics on steps of bacterial protein synthesis: Some new ribosomal inhibitors of translocation. J. Biol. Chem. 246, 7715–7722 (1971).PubMedGoogle Scholar
  28. 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
  29. RICHMAN, N. and J.W. BODLEY: The sites on the 50s ribosomal subunit with which elongation factors Tu and G interact are at least partially identical. Proc. Nat. Acad. Sci. USA 69, 686–689 (1972).PubMedCrossRefGoogle Scholar
  30. RICHTER, D.: Inability of E. coli ribosomes to interact simultaneously with the bacterial elongation factors EF-Tu and EF-G. Biochem. Biophys. Research Commun. 46, 1850–1856 (1972).CrossRefGoogle Scholar
  31. SOPORI, M.L. and P. LENGYEL: Components of the 50s ribosomal subunit involved in GTP cleavage. Biochem. Biophys. Research Commun. 46, 238–244 (1972).CrossRefGoogle Scholar
  32. SU, T.L.: Micrococcin, an anti-bacterial substance formed by a strain of micrococcus. Brit. J. Exp. Path. 29, 473–481 (1948).PubMedGoogle Scholar
  33. TANAKA, K., WATANABE, S., TERAOKA, H. and M. TAMAKI: Effect of siomycin on protein synthetic activity. Biochem. Biophys. Research Commun. 39, 1189–1193 (1970).CrossRefGoogle Scholar
  34. WEISBLUM, B7-and V. DEMOHN: Thiostrepton, an inhibitor of 50s ribosome subunit function. Biochem. Biophys. Research Commun. 101, 1073–1075 (1970a).Google Scholar
  35. WEISBLUM., B. and V. DEMOHN: Inhibition by thiostrepton of the formation of a ribosome-bound guanine nucleotide complex. FEBS Lett. 11, 149–152 (1970b).PubMedCrossRefGoogle Scholar
  36. WOODRUFF, H.B.: The physiology of antibiotic production: The role of the producing organism. Symp. Soc. Gen. Microbiol. 16, 22–46 (1966).Google Scholar

Copyright information

© Springer-Verlag/Wien 1975

Authors and Affiliations

  • Eric Cundliffe
  • Janet E. Beven
  • Peter D. Dixon

There are no affiliations available

Personalised recommendations