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Article|13 Dec 2023|OPEN
A biosynthetic network for protoberberine production in Coptis chinensis 
Linrui Wu1 , Binxin Zhao1 , Zixin Deng1 , Bin Wang2 and Yi Yu,1,2 ,
1Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuhan 430071, China
2State Key Laboratory of Non-Food Biomass and Enzyme Technology, Guangxi Academy of Sciences, Nanning 530007, China
*Corresponding author. E-mail: yu_yi@whu.edu.cn

Horticulture Research 11,
Article number: uhad259 (2024)
doi: https://doi.org/10.1093/hr/uhad259
Views: 20

Received: 06 Oct 2023
Accepted: 26 Nov 2023
Published online: 13 Dec 2023

Abstract

Protoberberine alkaloids are a group of tetracyclic isoquinoline compounds known for their well-established antimicrobial and anti-inflammatory properties. The richness and diversity of protoberberine alkaloids accumulated in the Coptis genus necessitate a comprehensive examination of the biosynthetic machinery to understand their ecological significance. Here, from Coptis chinensis we identified CcCYP719A1, which could install a methylenedioxy bridge on either ring A or ring D of the protoberberine backbone, thus diverging metabolite flux towards the biosynthesis of various protoberberine components. We also obtained CcCYP719A2 and CcCYP719A3, which underwent positive selection after diverging from CcCYP719A1 and maintained specific catalytic activity on ring D. Further, we resolved the biosynthetic pathway of jatrorrhizine by identifying two demethylases, which could also modulate protoberberine composition by removing the C-3 methyl group and methylenedioxy bridge of ring D, allowing demethylated metabolites to be redirected into different routes. Moreover, we characterized 2-O-methyltransferase CcOMT1 and flavin-dependent oxidase CcTHBO, respectively responsible for the commonly observed 2-O-methylation and aromatic ring-C assembly in protoberberine alkaloids. Overall, this study reveals an interconnected metabolite network from which diverse protoberberine alkaloids originate. It provides valuable insights into the existence of undiscovered protoberberine components, and paves the way for the targeted production of desired protoberberine components for potential therapeutic development.