News & Events


Harnessing Natural Diversity for New Synthetic Tools

Thursday, February 23, 2017 - 18:30 to 19:30
Zach Armstrong
Department of Chemistry, Centre for High Throughput Biology - Withers Group
Event Category: 
CBDG - Chemical Biology Discussion Group
Chemistry D200

    The use of biocatalysts in chemical synthesis offers advantages of increased selectivity and efficiency while reducing the amount of waste generated. Development of new or improved biocatalysts is achieved either by modifying an existing enzyme or by mining the vastly unexplored repertoire present in nature. Recently, access to affordable large-scale DNA synthesis has enabled the systematic sampling of natural diversity across an entire family of proteins. In this light, we aimed to harness a diverse set of glycoside hydrolase enzymes to help address a long-standing problem in the biological sciences: ready access to synthetic oligosaccharides.

    High-throughput screening of a synthetic gene-based library of expressing clones identified promising glycoside hydrolases which were capable of hydrolysing glycosides bearing amino and azido functionalities. A set of eight competent enzymes were then characterized and converted into glycosynthases, mutant hydrolases that may be capable of catalysing oligosaccharide synthesis. Mutant forms of seven of the eight hydrolases selected acted as competent glycosynthases yielding disaccharides, trisaccharides, glycolipids and inhibitors containing convenient azido or amino functional handles.