We report that simple glycoside donors can drastically shift the equilibria of glycosyltransferase-catalyzed reactions, transforming NDP-sugar formation from an endothermic to an exothermic process. To demonstrate the utility of this thermodynamic adaptability, we highlight the glycosyltransferase-catalyzed synthesis of 22 sugar nucleotides from simple aromatic sugar donors, as well as the corresponding in situ formation of sugar nucleotides as a driving force in the context of glycosyltransferase-catalyzed reactions for small-molecule glycodiversification. These simple aromatic donors also enabled a general colorimetric assay for glycosyltransfer, applicable to drug discovery, protein engineering and other fundamental sugar nucleotide-dependent investigations. This study directly challenges the general notion that NDP-sugars are 'high-energy' sugar donors when taken out of their traditional biological context.
|Number of pages||7|
|Journal||Nature Chemical Biology|
|State||Published - Oct 2011|
Bibliographical noteFunding Information:
This manuscript is dedicated to the late C. Richard Hutchinson for his pioneering contributions to engineered natural product glycosylation. We thank the School of Pharmacy Analytical Instrumentation Center (University of Wisconsin–Madison) for analytical support and G.J. Williams (North Carolina State University) for materials and helpful discussion. R.W.G. is an American Foundation for Pharmaceutical Education Pre-Doctoral Fellow. J.S.T. is a University of Wisconsin H.I. Romnes Fellow and holds the Laura and Edward Kremers Chair in Natural Products. This work was supported by US National Institutes of Health grant AI52218.
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology