Enzymatic Synthesis of Carbohydrate‐Containing Biomolecules

Abstract

AbstractAs important biomolecules in living organisms, carbohydrates have received increasing attention in recent years. Their important roles in biologic events are being continuously unraveled. The development of synthetic methodologies, including both chemical and enzymatic methods, contributes greatly to the advance of the field of glycoscience. The involvement of regio‐ and stereo‐selective enzymes in the synthesis of complex carbohydrate‐containing molecules has become an indispensable approach. Many enzymes involved in the biosynthesis and biodegradation of carbohydrates have been characterized and have been applied for the production of carbohydrate‐containing biomolecules, including oligosaccharides, polysaccharides, glycoproteins, glycolipids, and glycosylated natural products. A range of strategies for enzymatic synthesis have also been developed, such as protein engineering of glycosidases and glycosyltransferases by site‐directed mutagenesis or directed evolution, one‐pot multiple‐enzyme synthesis, sugar nucleotide regeneration, solid‐phase enzymatic synthesis, synthesis using immobilized enzymes, and cell‐based synthesis. Enzymatic synthesis will continue to play critical roles in obtaining complex carbohydrate‐containing biomolecules. Future efforts should focus on identifying synthetically useful enzymes such as those with flexible or novel substrate specificity and those that can form new bonds. This identification can be achieved by functional genomics and mutagenesis studies. Development of novel enzymatic synthetic methods is also critical to access diverse naturally occurring and non‐natural derivatives of carbohydrates and glycoconjugates.