Characterization of tylM3/tylM2 and mydC/mycB Pairs Required for Efficient Glycosyltransfer in Macrolide Antibiotic Biosynthesis

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• 作者：Charles E. Melan&ccedil ; on III ; Haruko Takahashi ; and Hung-wen Liu
• 刊名：Journal of the American Chemical Society
• 出版年：2004
• 出版时间：December 29, 2004
• 年：2004
• 卷：126
• 期：51
• 页码：16726 - 16727
• 全文大小：57K
• 年卷期：v.126,no.51(December 29, 2004)
• ISSN：1520-5126

文摘

The heterologous expression of tylM3 and mydC, two homologous genes of previously unknown function, along with genes encoding their respective partner glycosyltransferases, tylM2 and mycB, and the necessary sugar biosynthesis genes significantly enhances the glycosyltransferase activity in the engineered Streptomyces venezuelae host in which the native glycosyltransferase, desVII, has been inactivated. Both glycosyltransferases accept the endogenous 12-membered macrolide, 10-deoxymethynolide, or the exogenously fed 16-membered macrolide, tylactone. Five new compounds were generated using this expression system. This work suggests that the 13 other known TylM3/MydC/DesVIII homologues found in macrolide and anthracycline antibiotic clusters likely function as glycosyltransferase auxiliary proteins as well. These findings will greatly assist endeavors to generate new natural products in these pathways in a combinatorial fashion.