title: Using simple donors to drive the equilibria of glycosyltransferase-catalyzed reactions.
abstract: 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.
authors.affiliation: Pharmaceutical Sciences Division, School of Pharmacy, Wisconsin Center for Natural Products Research, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Gantt
authors.forename: Pauline
authors.initials: P
authors.lastname: Peltier-Pain
authors.forename: William J
authors.initials: WJ
authors.lastname: Cournoyer
authors.forename: Jon S
authors.initials: JS
authors.lastname: Thorson
mesh_terms: D055162:Biocatalysis; D005960:Glucosides / Q000737:chemistry* / Q000378:metabolism*; D016695:Glycosyltransferases / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis / Q000737:chemistry; D013237:Stereoisomerism; D013997:Time Factors
chemical_list: D005960:Glucosides; D009702:Nucleoside Diphosphate Sugars; D016695:Glycosyltransferases