Dataset Information

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 binds the deazaflavin cofactor coenzyme F420, and in vitro reconstitution of TpnL activity confirmed that this enzyme is an F420H2-dependent dehydropiperidine reductase. The identification of TpnL and its activity establishes the basis for the piperidine-containing series a thiopeptides, one of the five main structural groups of this diverse family of antibiotics.

SUBMITTER: Ichikawa H

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

REPOSITORIES: biostudies-literature

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Biosynthesis of the Thiopeptins and Identification of an F<sub>420</sub>H<sub>2</sub>-Dependent Dehydropiperidine Reductase.

Ichikawa Hiro H Bashiri Ghader G Kelly Wendy L WL

Journal of the American Chemical Society 20180817 34

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 tateyamensi ...[more]

PMID: 30118217

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Dataset Information

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

Publications

Biosynthesis of the Thiopeptins and Identification of an F<sub>420</sub>H<sub>2</sub>-Dependent Dehydropiperidine Reductase.

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