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The methymycin/pikromycin pathway: a model for metabolic diversity in natural product biosynthesis.

ABSTRACT: The methymycin/pikromycin (Pik) macrolide pathway represents a robust metabolic system for analysis of modular polyketide biosynthesis. The enzymes that comprise this biosynthetic pathway display unprecedented substrate flexibility, combining to produce six structurally diverse macrolide antibiotics in Streptomyces venezuelae. Thus, it is appealing to consider that the pikromycin biosynthetic enzymes could be leveraged for high-throughput production of novel macrolide antibiotics. Accordingly, efforts over the past decade have focused on the detailed investigation of the six-module polyketide synthase, desosamine sugar assembly and glycosyl transfer, and the cytochrome P450 monooxygenase that is responsible for hydroxylation. This review summarizes the advances in understanding of pikromycin biosynthesis that have been gained during the course of these investigations.

SUBMITTER: Kittendorf JD

PROVIDER: S-EPMC2843759 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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The methymycin/pikromycin pathway: a model for metabolic diversity in natural product biosynthesis.

Kittendorf Jeffrey D JD Sherman David H DH

Bioorganic & medicinal chemistry 20081105 6

The methymycin/pikromycin (Pik) macrolide pathway represents a robust metabolic system for analysis of modular polyketide biosynthesis. The enzymes that comprise this biosynthetic pathway display unprecedented substrate flexibility, combining to produce six structurally diverse macrolide antibiotics in Streptomyces venezuelae. Thus, it is appealing to consider that the pikromycin biosynthetic enzymes could be leveraged for high-throughput production of novel macrolide antibiotics. Accordingly, e ...[more]

PMID: 19027305

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