Sialoglycan engineering empowered by recombinant sialyltransferases

Glycans that terminate in monosaccharides belonging to the sialic acid family of sugars regulate myriad biological processes and are increasingly being recognized as important immunoregulatory targets. These sialoglycans are biosynthesized by sialyltransferase enzymes which catalyze the transfer of CMP-sialic acid to an acceptor glycan. Many sialyltransferases display remarkable substrate tolerance and have therefore been used to incorporate chemically derivatized sialic acids into a variety of glycan structures for diverse applications involving detection and engineering of specific glycans. Sialyltransferase-mediated glycoengineering approaches have been leveraged in chemoenzymatic glycan synthesis and more recently, for sialoglycan assembly on living cell surfaces through a technique called selective exo-enzymatic labeling (SEEL). Here, we highlight the specific chemical modifications of sialic acids that have been shown compatible with diverse recombinant sialyltransferases used in both chemoenzymatic and SEEL workflows. These technologies enabled by sialyltransferases are enhancing our understanding of sialoglycan biology and are well poised to further illuminate the roles of sialoglycans in human health and disease.