Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 17, Issue 6, Pages 2137-2146Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2008.10.082
Keywords
Polyketides; PKS; Natural products; Biosynthesis; Pikromycin
Funding
- National Institutes of Health [GM48562, GM078553]
- Hans and Ella McCollum Vahlteich Research Fund
- NIH [GM075641]
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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. (C) 2008 Elsevier Ltd. All rights reserved.
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