Biosynthesis of the Thiopeptins and Identification of an F₄₂₀H₂-Dependent Dehydropiperidine Reductase.

ABSTRACT: Thiopeptins are highly decorated thiopeptide antibiotics similar in structure to thiostrepton A and harbor two unusual features. All thiopeptins contain a thioamide, a rare moiety among natural products, and a subset of thiopeptins present with a piperidine in the core macrocycle rather than the more oxidated dehydropiperidine or pyridine rings typically observed in the thiopeptides. Here, we report the identification of the thiopeptin biosynthetic gene ( tpn) cluster in Streptomyces tateyamensis and the gene product, TpnL, which shows sequence similarity to (deaza)flavin-dependent oxidoreductases. Heterologous expression of TpnL in the thiostrepton A producer Streptomyces laurentii led to the production of a piperidine-containing analogue. Binding studies revealed that TpnL preferentially

SUBMITTER: Ichikawa H 

PROVIDER: S-EPMC6193465 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature