Abstract
Aporphine alkaloids have diverse pharmacological activities;however,our understanding of their biosynthesis is relatively limited.Previous studies have classified aporphine alkaloids into two cat-egories based on the configuration and number of substituents of the D-ring and have proposed preliminary biosynthetic pathways for each cat-egory.In this study,we identified two specific cy-tochrome P450 enzymes(CYP80G6 and CYP80Q5)with distinct activities toward(S)-configured and(R)-configured substrates from the herbaceous perennial vine Stephania tetrandra,shedding light on the biosynthetic mechanisms and stereo-chemical features of these two aporphine alkaloid categories.Additionally,we characterized two CYP719C enzymes(CYP719C3 and CYP719C4)that catalyzed the formation of the methylenedioxy bridge,an essential pharmacophoric group,on the A-and D-rings,respectively,of aporphine al-kaloids.Leveraging the functional characterization of these crucial cytochrome P450 enzymes,we re-constructed the biosynthetic pathways for the two types of aporphine alkaloids in budding yeast(Saccharomyces cerevisiae)for the de novo pro-duction of compounds such as(R)-glaziovine,(S)-glaziovine,and magnoflorine.This study pro-vides key insight into the biosynthesis of aporphine alkaloids and lays a foundation for producing these valuable compounds through synthetic biology.
维普
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