S189: Generation of Thiostrepton Derivatives

Thiostrepton and other thiopeptide metabolites are structurally complex peptide-based metabolites that are notable for their potent antibacterial and antimalarial activities. Despite their promising medicinal properties, development of a clinically useful thiopeptide will ultimately require manipulation of their structures to improve upon the poor water solubility of the naturally-occurring compounds. Two possible approaches to solve this problem include semisynthetic modification of isolated thiopeptides and biosynthetic engineering to generate designer thiopeptide structures. Recently, thiopeptides were revealed to be products of a ribosomally-synthesized peptide subject to extensive posttranslational modifications. We report here the development of a platform to generate thiostrepton variants by using the thiostrepton-producing bacterium, Streptomyces laurentii.