earticle

영어

Post-biosynthesis modifications of natural products (NPs) provides opportunity to bring chemical diversity to the parent molecule. Such modifications usually play vital roles in executing biological activities of the molecules. Thus, engineering of molecules by diverse post-modifications is increasingly becoming a tool to design or produce novel biologically potent biologics. To develop the rapid and sustainable system for the production of different flavonoid glycosides, central metabolic pathway for the production of pool of UDP-0-glucose, UDP-0-xylose, TDP-L -rhamnose, TDP-0-viosamine, TOP 4-amino 4,6-dideoxy-D-galactose, and TOP 3-amino 3,6-dideoxy-D-galactose was engineered in E. coli BL21 (DE3) cells. Different glycosyltransferases were engaged to transfer sugar moieties to aglycones. Several flavonoids and isoflavonoid glycosides including natural and non-natural o- and C- glycosides were produced by microbial cell fermentation. In a different approach of enzymatic biosynthesis, a number of glycodiversified flavonoids were generated using several NDP-sugars and GTs in vitro. As a result, glycodiversified resveratrol, flavonol, epothilone A, mupirocin conjugated with glucose, galactose, 2-deoxyglucose, viosamine, rhamnose, and fucose sugars were produced. Multiple glycosides of other flavonoids, isoflavonoids, chalcones, stilbenes, xanthonoids, anthraquinones, anthracyclines, and terpenoids were also generated with significantly high yield. Some of the selected glycosides exhibited promising anticancer, antibacterial, immunomodulatory, anti-inflammatory, antioxidant, and anti-asthmatic activities in in vitro and in vivo mouse models. This approach of microbial and enzymatic synthesis of novel glycosides derivatives of NPs using highly flexible and promiscuous enzymes from diverse sources opened up possibility of development of new molecules with better stability, bioavailability, and novel biological activity.