DOI: 10.1093/hr/uhad259 ISSN: 2052-7276

A biosynthetic network for protoberberine production in Coptis chinensis

Linrui Wu, Binxin Zhao, Zixin Deng, Bin Wang, Yi Yu
  • Horticulture
  • Plant Science
  • Genetics
  • Biochemistry
  • Biotechnology


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 Coptis genus necessitate a comprehensive examination of the biosynthetic machinery to understand their ecological significance. Here, from Coptis chinensis we identified CcCYP719A1 that could install methylenedioxy bridge on either ring-A or ring-D of protoberberine backbone, thus diverging metabolite flux towards the biosynthesis of various protoberberine components. We also obtained CcCYP719A2 and CcCYP719A3 that 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 through 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.

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