Synthesis of Glycosides by Glycosynthases.

Jörg Pietruszka,Marc Hayes

doi:10.3390/molecules22091434

Abstract

The many advances in glycoscience have more and more brought to light the crucial role of glycosides and glycoconjugates in biological processes. Their major influence on the functionality and stability of peptides, cell recognition, health and immunity and many other processes throughout biology has increased the demand for simple synthetic methods allowing the defined syntheses of target glycosides. Additional interest in glycoside synthesis has arisen with the prospect of producing sustainable materials from these abundant polymers. Enzymatic synthesis has proven itself to be a promising alternative to the laborious chemical synthesis of glycosides by avoiding the necessity of numerous protecting group strategies. Among the biocatalytic strategies, glycosynthases, genetically engineered glycosidases void of hydrolytic activity, have gained much interest in recent years, enabling not only the selective synthesis of small glycosides and glycoconjugates, but also the production of highly functionalized polysaccharides. This review provides a detailed overview over the glycosylation possibilities of the variety of glycosynthases produced until now, focusing on the transfer of the most common glucosyl-, galactosyl-, xylosyl-, mannosyl-, fucosyl-residues and of whole glycan blocks by the different glycosynthase enzyme variants.

Highlights

With the increasingly growing knowledge of the major role glycosides and glycoconjugates play in biological processes, the demand for simple methods for the synthesis of defined glycosides is constantly rising
Though most exo-glycosidase derived glycosynthases are limited to glycosyl transfer glycosylation of non-glycosylated flavonoid structures (e.g., 21 and 22, Scheme 3) [30]. The former to glycosides, Yang et al utilized the glycosynthase of HiCel7B, HiCel7B E197S in the glycosylation endo-cellulase catalyzed the transfer of lactosyl fluoride (23, LacF) with high selectivity to the of non-glycosylated flavonoid structures (e.g., 21 and 22, Scheme 3) [30]
The direct comparison of enzymatic glycosylation reactions compared to the chemical paths is difficult due to the additional protection and deprotection as well as possible modification steps needed after chemical glycosylation

Summary

Introduction

With the increasingly growing knowledge of the major role glycosides and glycoconjugates play in biological processes, the demand for simple methods for the synthesis of defined glycosides is constantly rising. Their glycosidic structures is accomplished by the enzyme group of glycosyltransferases These enzymes in biocatalysis has been extensively researched, but is still limited for a large scale by the high cost of transfer activated sugar nucleotide donor molecules selectively onto an acceptor molecule. Alternative carbohydrate active enzymes are glycohydrolases organisms [8] This group of enzymes naturally degrade glycosidic structures and are defined glycosidases, of which a high variety are readily available due to their occurrence in the metabolicinto two pathways groups depending on their catalytic mechanism Residue Inverting in the resulting in a retention the anomeric configuration the substrate in and the yielded enzymes active site resulting in a retention of the anomeric configuration of the substrate in the yielded glycosidases in comparison follow a single displacement mechanism with two catalytic acid/base product. This review will focus on the synthesis of glycosides employing glycosynthase methods, only, summarizing in each section the findings of a specific glycosyl residue giving an overview of described products, which have been synthesized, rather than focusing on the production of the glycosynthase itself

Glucosynthases

Direct glycosylation flavonoids21

Galactosynthases

Synthesis of theofmethyl umbelliferone derivative of the type blood

Synthesis of the yield glycolipid lyso-G

Xylosynthases

Synthesis

Production

Combinatorial

Mannosynthases

Glycosynthase Variants of endo-β-N-Acetylglucosaminidases

GlcNAc-oxazoline