thiostrepton

Thiostrepton is a thiopeptide antibiotic produced primarily by actinomycetes of the genus Streptomyces. It is a large, highly modified macrocyclic peptide characterized by a central macrocycle containing multiple thiazole rings and a quinaldic acid moiety. Thiostrepton is active primarily against Gram-positive bacteria and is notable for its potency, though its use in humans is limited by toxicity. It is employed mainly in topical veterinary formulations and in laboratory settings.

Thiostrepton binds to the 50S ribosomal subunit at the GTPase-associated center near the L11 protein and 23S rRNA, inhibiting the activity of elongation factors EF-Tu and EF-G during translation, thereby blocking translocation. The result is primarily bacteriostatic inhibition of protein synthesis.

As a natural product, thiostrepton is a RiPP produced by Streptomyces species; its biosynthesis involves ribosomal synthesis of a precursor peptide followed by extensive post-translational modifications that generate the thiazole rings, dehydroamino acid residues, and the macrocycle. This class of antibiotics is known as thiopeptides.

Resistance can arise through mutations in ribosomal proteins or rRNA that reduce binding, or by acquisition of thiostrepton-resistance genes (tsr). In molecular biology, tsr is used as a selectable marker in Gram-positive bacteria.