Exploiting the reversibility of natural product glycosyltransferase-catalyzed reactions |
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Authors: | Zhang Changsheng Griffith Byron R Fu Qiang Albermann Christoph Fu Xun Lee In-Kyoung Li Lingjun Thorson Jon S |
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Affiliation: | Laboratory for Biosynthetic Chemistry, Pharmaceutical Sciences Division, School of Pharmacy, National Cooperative Drug Discovery Group Program, University of Wisconsin (UW)-Madison, 777 Highland Avenue, Madison, WI 53705-2222, USA. |
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Abstract: | Glycosyltransferases (GTs), an essential class of ubiquitous enzymes, are generally perceived as unidirectional catalysts. In contrast, we report that four glycosyltransferases from two distinct natural product biosynthetic pathways-calicheamicin and vancomycin-readily catalyze reversible reactions, allowing sugars and aglycons to be exchanged with ease. As proof of the broader applicability of these new reactions, more than 70 differentially glycosylated calicheamicin and vancomycin variants are reported. This study suggests the reversibility of GT-catalyzed reactions may be general and useful for generating exotic nucleotide sugars, establishing in vitro GT activity in complex systems, and enhancing natural product diversity. |
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