Insights into functional divergence, catalytic versatility and specificity of small molecule glycosyltransferases.

Glycosylation is one of the most fundamental biochemical processes in cells. It plays crucial roles in diversifying plant natural products for structures, bioavailability and bioactivity, and thus, renders the glycosylated compounds valuable as food additives, nutraceuticals and pharmaceuticals. Moreover, glycosylated compounds impact plant growth, development and stress response. Therefore, understanding the biochemical function of the glycosyltransferases (GTs) is crucial to the elucidation of natural product biosynthetic pathways, improving plant traits and development of processes for industrially-important compounds. UDP-dependent glycosyltransferases (UGTs) that belong to the glycosyltransferase family-1 (GT1) and catalyze the transfer of glycosyl moieties from UDP-sugars to various small molecules, are the key players in natural product glycosylation. Recent studies also found the involvement of non-canonical cellulose synthase-like (CesAs) and glycosyl hydrolase (GH) family enzymes in the glycosylation of plant specialized metabolites. Decades of research on GTs provided critical insights into catalytic mechanism, substrate/product specificity and catalytic promiscuity, but biochemical function and physiological roles of GTs in majority of the natural product biosynthetic pathways remain to be understood. It is also important to redefine high-throughput strategies of GT mining to uncover novel biochemical function, considering that GTs are the large superfamily members in plants and other organisms. This review underscores the roles of GTs in small molecule glycosylation, plant development and stress responses, highlighting the catalytic versatility and substrate/product specificity of GTs in shaping plant metabolic diversity, and discusses the emerging strategies for mining of uncharacterized GTs to unravel biochemical and physiological functions and to elucidate natural product biosynthetic pathways.