Griseorhodins D鈥揊, Neuroactive Intermediates and End Products of Post-PKS Tailoring Modification in Griseorhodin Biosynthesis

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• 作者：Zhenjian Lin ; Malcolm M. Zachariah ; Lenny Marett ; Ronald W. Hughen ; Russell W. Teichert ; Gisela P. Concepcion ; Margo G. Haygood ; Baldomero M. Olivera ; Alan R. Light ; Eric W. Schmidt
• 刊名：Journal of Natural Products
• 出版年：2014
• 出版时间：May 23, 2014
• 年：2014
• 卷：77
• 期：5
• 页码：1224-1230
• 全文大小：344K
• 年卷期：v.77,no.5(May 23, 2014)
• ISSN：1520-6025

文摘

The griseorhodins belong to a family of extensively modified aromatic polyketides that exhibit activities such as inhibition of HIV reverse transcriptase and human telomerase. The vast structural diversity of this group of polyketides is largely introduced by enzymatic oxidations, which can significantly influence the bioactivity profile. Four new compounds, griseorhodins D鈥揊, were isolated from a griseorhodin producer, Streptomyces sp. CN48+, based upon their enhancement of calcium uptake in a mouse dorsal root ganglion primary cell culture assay. Two of these compounds, griseorhodins D1 and D2, were shown to be identical to the major, previously uncharacterized products of a grhM mutant in an earlier griseorhodin biosynthesis study. Their structures enabled the establishment of a more complete hypothesis for the biosynthesis of griseorhodins and related compounds. The other two compounds, griseorhodins E and F, represent new products of post-polyketide synthase tailoring in griseorhodin biosynthesis and showed significant binding activity in a human dopamine active transporter assay.