Research & Teaching Faculty

Glycosynthases: Mutant glycosidases for glycoside synthesis

TitleGlycosynthases: Mutant glycosidases for glycoside synthesis
Publication TypeJournal Article
Year of Publication2002
AuthorsWilliams, SJ, Withers, SG

Glycosynthases are engineered mutant glycosidases that catalyse the formation of a glycosidic bond from a glycosyl donor and an acceptor alcohol. They are constructed by mutation of the enzymic nucleophile of a retaining glycosidase to a small non-nucleophilic residue. To date, five glycosynthases have been reported capable of synthesizing a range of beta-glycosidic linkages. Methods to integrate protecting groups into glycosynthase-mediated glycosylations have been developed that broaden their applicability and enable finer control over product formation. Mutagenesis studies have improved the catalytic power of the original Abg glycosynthase, and a general methodology has been developed that allows the rapid screening of libraries of mutant glycosynthases for catalysts with improved activity. A method for determining aglycon substrate specificity has been developed to define the limits of substrate variation tolerated by a parent glycosidase and thence the derived glycosynthase. Together, these developments portend a bright future for the discovery of new glycosynthases and their widespread application as catalysts to assist in the rapid and efficient assembly of complex glycoconjugates.