Catalytic Analysis of the Validamycin Glycosyltransferase (ValG) and Enzymatic Production of 4′′-epi-Validamycin A

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• 作者：Hui Xu ; Kazuyuki Minagawa ; Linquan Bai ; Zixin Deng ; Taifo Mahmud
• 刊名：Journal of Natural Products
• 出版年：2008
• 出版时间：July 2008
• 年：2008
• 卷：71
• 期：7
• 页码：1233-1236
• 全文大小：164K
• 年卷期：v.71,no.7(July 2008)
• ISSN：1520-6025

文摘

ValG is a glycosyltransferase (GT) that is responsible for the glucosylation of validoxylamine A to validamycin A. To explore the potential utilization of ValG as a tool for the production of validamycin analogues, a number of nucleotidyldiphosphate-sugars were evaluated as alternative substrates for ValG. The results indicated that in addition to its natural substrate, UDP-glucose, ValG also efficiently utilized UDP-galactose as sugar donor and resulted in the production of an unnatural compound, 4′′-epi-validamycin A. The new compound demonstrated a moderate growth inhibitory activity against the plant fungal pathogen Rhizoctonia solani (=Pellicularia sasakii). A comparative analysis of ValG with its homologous proteins revealed that ValG contains an unusual DTG motif, in place of the DXD motif proposed for metal ion binding and/or NDP-sugar binding and commonly found in other glycosyltransferases. Site-directed mutagenesis of the DTG motif of ValG to DCD altered its preferences for metal ion binding, but did not seem to affect its substrate specificity.