A Systematic Investigation of the Synthetic Utility of Glycopeptide Glycosyltransferases
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- 作者：Markus Oberthü ; r ; Catherine Leimkuhler ; Ryan G. Kruger ; Wei Lu ; Christopher T. Walsh ; and Daniel Kahne
- 刊名：Journal of the American Chemical Society
- 出版年：2005
- 出版时间：August 3, 2005
- 年：2005
- 卷：127
- 期：30
- 页码：10747 - 10752
- 全文大小：133K
- 年卷期：v.127,no.30(August 3, 2005)
- ISSN：1520-5126
文摘
Glycosyltransferases involved in the biosynthesis of bacterial secondary metabolites may beuseful for the generation of sugar-modified analogues of bioactive natural products. Some glycosyltransferases have relaxed substrate specificity, and it has been assumed that promiscuity is a feature of theclass. As part of a program to explore the synthetic utility of these enzymes, we have analyzed the substrateselectivity of glycosyltransferases that attach similar 2-deoxy-L-sugars to glycopeptide aglycons of thevancomycin-type, using purified enzymes and chemically synthesized TDP 
-2-deoxy-L-sugar analogues.We show that while some of these glycopeptide glycosyltransferases are promiscuous, others tolerateonly minor modifications in the substrates they will handle. For example, the glycosyltransferases GtfCand GtfD, which transfer 4-epi-L-vancosamine and L-vancosamine to C-2 of the glucose unit of vancomycinpseudoaglycon and chloroorienticin B, respectively, show moderately relaxed donor substrate specificitiesfor the glycosylation of their natural aglycons. In contrast, GtfA, a transferase attaching 4-epi-L-vancosamineto a benzylic position, only utilizes donors that are closely related to its natural TDP sugar substrate. Ourdata also show that the spectrum of donors utilized by a given enzyme can depend on whether the naturalacceptor or an analogue is used, and that GtfD is the most versatile enzyme for the synthesis of vancomycinanalogues.
-2-deoxy-L-sugar analogues.We show that while some of these glycopeptide glycosyltransferases are promiscuous, others tolerateonly minor modifications in the substrates they will handle. For example, the glycosyltransferases GtfCand GtfD, which transfer 4-epi-L-vancosamine and L-vancosamine to C-2 of the glucose unit of vancomycinpseudoaglycon and chloroorienticin B, respectively, show moderately relaxed donor substrate specificitiesfor the glycosylation of their natural aglycons. In contrast, GtfA, a transferase attaching 4-epi-L-vancosamineto a benzylic position, only utilizes donors that are closely related to its natural TDP sugar substrate. Ourdata also show that the spectrum of donors utilized by a given enzyme can depend on whether the naturalacceptor or an analogue is used, and that GtfD is the most versatile enzyme for the synthesis of vancomycinanalogues.