Advances in Enzymatic Glycoside Synthesis

A robust platform for facile defined glycan synthesis does not exist. Yet the need for such technology has never been greater as researchers seek to understand the full scope of carbohydrate function, stretching beyond the classical roles of structure and energy storage to encompass highly nuanced cell signaling events. To comprehensively explore and exploit the full diversity of carbohydrate functions, we must first be able to synthesize them in a controlled manner. Toward this goal, traditional chemical syntheses are inefficient while nature’s own synthetic enzymes, the glycosyl transferases, can be challenging to express and expensive to employ on scale. Glycoside hydrolases represent a pool of glycan processing enzymes that can be either used in a transglycosylation mode or, better, engineered to function as “glycosynthases,” mutant enzymes capable of assembling glycosides. Glycosynthases grant access to valuable glycans that act as functional and structural probes or indeed as inhibitors and therapeutics in their own right. The remodelling of glycosylation patterns in therapeutic proteins via glycoside hydrolases and their mutants is an exciting frontier in both basic research and industrial scale processes.