Inactivation of the urdGT2 Gene, Which Encodes a Glycosyltransferase Responsible for the C-Glycosyltransfer of Activated D-Olivose, Leads to Formation of the Novel Urdamy

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• 作者：Eva Kü ; nzel ; Bettina Faust ; Carsten Oelkers ; Ulrike Weissbach ; Daniel W. Bearden ; Gabriele Weitnauer ; Lucia Westrich ; Andreas Bechthold ; and Jü ; rgen Rohr
• 刊名：Journal of the American Chemical Society
• 出版年：1999
• 出版时间：December 8, 1999
• 年：1999
• 卷：121
• 期：48
• 页码：11058 - 11062
• 全文大小：143K
• 年卷期：v.121,no.48(December 8, 1999)
• ISSN：1520-5126

文摘

A targeted search for glycosyltransferase (GT) encoding genes in the gene cluster of the urdamycinA producer Streptomyces fradiae Tü2717 resulted in the discovery of urdGT2, a GT encoding gene locatedapproximately 7 kb downstream of the minimal polyketide synthase (PKS) encoding genes. Subsequentinactivation of this gene created a mutant strain, which produces completely different metabolites than thewild-type strain, consisting of the three new urdamycins I, J, and K. Their structures provide new insight intothe important C-glycosyl-transfer step of the urdamycin biosynthetic pathway. The structures indicate that thecorresponding gene product UrdGT2 catalyzes the C-glycosyl transfer of activated D-olivose to an angucyclinoneprecursor, which already bears the angular 12b-OH group. The structures of the new urdamycins could nothave arisen without the involvement of substrate flexible post-PKS modifying genes, i.e., glycosyltransferasesand oxidoreductases. This work proves that targeted gene disruption experiments can lead to novel biologicallyactive "unnatural" natural products, which arise through a formerly nonactivated shunt pathway. This approachis especially fruitful in work toward antitumor drugs. Urdamycin J shows a good anticancer activity in in vitrotests.