Thiopeptides

This chapter reviews thiopeptides. Thiostrepton is produced in low quantities by Streptomyces azureus ATCC 14921 and Streptomyces hawaiiensis ATCC 12236, and overproduced by Streptomyces laurentii ATCC 31255; it is used as a topical veterinary antibiotic and as a selective agent in recombinant DNA experiments with streptomycetes. Nosiheptide is produced by Streptomyces actuosus ATCC 25421, Streptomyces sp. ATCC 31463, and Streptomyces glaucogriseus NRRL LL-BP189; it is used as an animal feed additive to promote weight gain. Thiostrepton inhibits protein synthesis by binding to 23S ribosomal RNA (rRNA) and ribosomal protein L-l 1 to block the GTP hydrolysis activities of the 50S ribosomal subunit. The thiopeptide antibiotics also interfere with synthesis of the stringent response factor ppGpp, and expression of the thiostrepton resistance gene prevents thiostrepton from inhibiting ppGpp formation. Thiostrepton resistance is conferred by a methylase that specifically methylates adenosine-1067 of 23S rRNA to produce 2'-0-methyladenosine; thiostrepton does not bind 23S rRNA methylated in this position. The mechanisms for nosiheptide activity and resistance appear to be the same as for thiostrepton.