Recent Developments in Glycoside Synthesis with Glycosynthases and Thioglycoligases

Bojana Rakić; Stephen G. Withers

doi:10.1071/CH09059

RESEARCH FRONT

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Recent Developments in Glycoside Synthesis with Glycosynthases and Thioglycoligases

Bojana Rakić ^A and Stephen G. Withers ^A ^B

+ Author Affiliations

- Author Affiliations

^A Centre for High-Throughput Biology and Department of Chemistry, 2036 Main Mall, University of British Columbia, Vancouver V6T 1Z1, Canada.

^B Corresponding author. Email: withers@chem.ubc.ca

Bojana Rakić obtained her B.Sc. in organic synthesis under the supervision of Professor Radomir Saičić, at the University of Belgrade, Serbia. On receiving an international fellowship, she moved to Canada and obtained her Ph.D. in 2007 at the University of Ottawa/National Research Council of Canada under the supervision of Professor John Pezacki, where she worked on small-molecule effects on the hepatitis C virus. Currently, she is a Postdoctoral Fellow at the University of British Columbia with Professor Stephen Withers, where she works on developing chemical biology approaches to study the function of mammalian sialyltransferases.

Steve Withers was trained (B.Sc. and Ph.D.) at the University of Bristol, UK, where he obtained his Ph.D. with Dr Michael Sinnott. He moved to Canada as a postdoctoral fellow, applying heteronuclear NMR to the study of enzymatic catalysis with Drs Brian Sykes and Neil Madsen in the Department of Biochemistry at the University of Alberta. In 1982, he moved to the University of British Columbia (UBC) as Assistant Professor of Chemistry. He now holds the Khorana Chair of Chemistry and Biochemistry at UBC and serves as the Director of CHiBi, the Centre for High-Throughput Biology at UBC.

Australian Journal of Chemistry 62(6) 510-520 https://doi.org/10.1071/CH09059
Submitted: 28 January 2009 Accepted: 31 March 2009 Published: 10 June 2009

Abstract

Glycosynthases are hydrolytically incompetent engineered glycosidases that catalyze the high-yielding synthesis of glycoconjugates from glycosyl fluoride donor substrates and appropriate acceptors. Glycosynthases from more than 10 glycoside hydrolase families have now been generated, allowing the synthesis of a wide range of oligosaccharides. Recent examples include glycosynthase-mediated syntheses of xylo-oligosaccharides, xyloglucans, glycolipids, and aryl glycosides. Glycosynthases have also now been generated from inverting glycosidases, increasing the range of enzyme scaffolds. Improvement of glycosynthase activity and broadening of specificity has been achieved through directed evolution approaches, and several novel high-throughput screens have been developed to allow this. Finally, metabolically stable glycoside analogues have been generated using another class of mutant glycosidases: thioglycoligases. Recent developments in all these aspects are discussed.

Acknowledgements

The authors thank the Natural Sciences and Engineering Research Council of Canada for financial support.

References

Recent Developments in Glycoside Synthesis with Glycosynthases and Thioglycoligases

Abstract

Acknowledgements

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