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.
저자
Ramesh Prasad Pandey [ Department of Pharmaceutical Engineering and Biotechnology, DepartmentoflifeScienceand Biochemical Engineering, Sun Moon University ]
PrakashParajuli [ DepartmentoflifeScienceand Biochemical Engineering, Sun Moon University ]
AnilShrestha [ DepartmentoflifeScienceand Biochemical Engineering, Sun Moon University ]
JaeKyungSohng [ Department of Pharmaceutical Engineering and Biotechnology, DepartmentoflifeScienceand Biochemical Engineering, Sun Moon University ]
본 학회는 화학, 생화학, 분자생물학, 미생물학, 식품공학, 의학, 약학, 유전공학 및 생물공학, 환경 및 기타 공업 등 전 분야의 탄수화물관련 이론과 기술을 연구 발전시키고 산학협동을 통해 이를 보급하여 국내 관련 산업의 발전 및 국민생활의 과학화에 기여하고자 하며, 이러한 목표와 비젼의 실현을 위해 회원들이 적극적인 참여와 활동을 전개하고자 한다.