Advances in engineering UDP-sugar supply for recombinant biosynthesis of glycosides in microbes

Plant glycosides are of great interest for industries. Glycosylation of plant secondary metabolites can greatly improve their solubility, biological activity, or stability. This allows some plant glycosides to be used as food additives, cosmetic products, health products, antisepsis and anti-cancer drugs. With the continuous expansion of market demand, a variety of biological fermentation technologies has emerged. This review focuses on recombinant microbial biosynthesis of plant glycosides, which uses UDP-sugars as precursors, and summarizes various strategies to increase the yield of glycosides with a key concentration on UDP-sugar supply based on four aspects, i.e., gene overexpression, UDP-sugar recycling, mixed fermentation, and carbon co-utilization. Meanwhile, the application potential and advantages of various techniques are introduced, which provide guidance to the development of high-yield strains for recombinant microbial production of plant glycosides. Finally, the technical challenges of glycoside biosynthesis are pointed out with discussions on future directions of improving the yield of recombinantly synthesized glycosides.