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From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Isolation, structure and biological activities of platensimycin B4 from Streptomyces platensis
Chaowei Zhang1, John Ondeyka, Ziqiang Guan
1Merck Research Laboratories, Rahway, NJ 07065, USA.
Abstract:
Platensimycin and platencin are inhibitors of FabF and FabF/H bacterial fatty acid synthesis enzymes, respectively. Discovery of natural congeners provides one of the ways to understand the relationship of chemical structure and biological function. Efforts to discover the natural analogs of platensimycin by chemical screening led to the isolation of platensimycin B(4), a glucoside congener of platensimycin. This analog showed significantly attenuated activity and critically defined the limited binding space around the aromatic ring and established the importance of the free phenolic and carboxyl group for the activity.
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