Platensimycin and Platencin Congeners from Streptomyces platensis

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• 作者：Chaowei Zhang ; John Ondeyka ; Kithsiri Herath ; Hiranthi Jayasuriya ; Ziqiang Guan ; Deborah L. Zink ; Lisa Dietrich ; Bruce Burgess ; Sookhee N. Ha ; Jun Wang ; Sheo B. Singh
• 刊名：Journal of Natural Products
• 出版年：2011
• 出版时间：March 25, 2011
• 年：2011
• 卷：74
• 期：3
• 页码：329-340
• 全文大小：988K
• 年卷期：v.74,no.3(March 25, 2011)
• ISSN：1520-6025

文摘

Platensimycin (1a) and platencin (2) are inhibitors of FabF and FabF/H bacterial fatty acid synthase. The discovery of natural congeners is an approach that can render a better understanding of the structure鈭抐unction relationships of complex natural products. The isolation and structure elucidation of nine new congeners (11鈭?b>20) of platensimycin and platencin are described from a fermentation broth of Streptomyces platensis. These hydroxylated congeners are likely derived by cytochrome P450 oxidation of the terpenoid units post-cyclization. Polar groups in the terpenoid portion of the molecule produce negative interactions with the hydrophobic pocket of FabF, resulting in poor activities. However, the discovery of these compounds serves an important purpose, not only to understand structure鈭抐unction relationships, which cannot be easily accessed by chemical modification, but also to provide access to compounds that could be used for structural identification/confirmation of the oxidative trace metabolites produced in vivo during animal experiments.