药用植物中单萜吲哚生物碱的代谢工程调控策略研究进展OA

Monoterpenoid indole alkaloids(MIAs),a class of natural products with remarkable pharmacological activities,are widely distributed in multiple medicinal plant species of the Apocynaceae family.Significant application values of these compounds have been demonstrated in the treatment of anti-tumor,cardiovascular and cerebrovascular diseases,as well as central nervous system diseases.The biosynthetic pathways of MIAs in four representative medicinal plants,Catharanthus roseus,Camptotheca acuminata,Uncaria spp.and Melodinus yunnanensis.are systematically reviewed.The synthetic process of the common precursor strictosidine and the formation mechanism of product structural diversification are emphatically expounded,and the enzymatic functional differentiation and evolutionary path differences among different species in precursor generation and downstream modification are revealed.The core strategies of current metabolic engineering for regulating MIA biosynthesis are further summarized,including regulation of endogenous and exogenous enzyme expression,transcription factor regulation,gene silencing and editing,transporter-mediated regulation,and hormonal regulation,which provides theoretical support for efficient synthesis of high-value MIAs.In conclusion,the metabolic network of MIAs is complex and sophisticated.The combination of single-cell omics and synthetic biology technologies will open up new directions for the development and application of novel medicinal alkaloids.