Metabolic Engineering of Glycans

Metabolic engineering of glycosylation exploits cellular metabolism and associated enzymes to modify the structures of glycans. This chemical approach has been particularly powerful for the visualization, characterization, and perturbation of glycoproteins in cells and even living multicellular organisms. In this article, we divide the broad technique of metabolic engineering into two general categories. The first category, metabolic reporters, are analogs of monosaccharides that bear small chemical reactive groups that are utilized in two steps. In the first step, monosaccharide analogs are accepted by biosynthetic pathways and glycosyltransferases to be incorporated into various glycoproteins. In a second chemical step, these reactive groups undergo bioorthogonal reactions for the attachment of visualization or affinity tags. In the second category, monosaccharide analogs are chemically modified to create inhibitors of specific glycosylation pathways. Similar to the metabolic reporters, these inhibitors take advantage of biosynthetic pathways to generate mechanistic inhibitors or chain terminators of different types of glycans. Together metabolic reporters and metabolic chemical inhibitors provide powerful tools for probing glycosylation.