Controlled processivity in glycosyltransferases: A way to expand the enzymatic toolbox

Abstract

Glycosyltransferases (GT) catalyse the biosynthesis of complex carbohydrates which are the most abundant group of molecules in nature. They are involved in several key mechanisms such as cell signalling, biofilm formation, host immune system invasion or cell structure and this in both prokaryotic and eukaryotic cells. As a result, research towards complete enzyme mechanisms is valuable to understand and elucidate specific structure-function relationships in this group of molecules. In a next step this knowledge could be used in GT protein engineering, not only for rational drug design but also for multiple biotechnological production processes, such as the biosynthesis of hyaluronan, cellooligosaccharides or chitooligosaccharides. Generation of these poly- and/or oligosaccharides is possible due to a common feature of several of these GTs: processivity. Enzymatic processivity has the ability to hold on to the growing polymer chain and some of these GTs can even control the number of glycosyl transfers. In a first part, recent advances in understanding the mechanism of various processive enzymes are discussed. To this end, an overview is given of possible engineering strategies for the purpose of new industrial and fundamental applications. In the second part of this review, we focused on specific chain length-controlling mechanisms, i.e., key residues or conserved regions, and this for both eukaryotic and prokaryotic enzymes.

Keywords: Glycosyltransferases; Molecular ruler mechanism; Processivity; Protein engineering.