首页|Identification of the cytochrome P450s responsible for the biosynthesis of two types of aporphine alkaloids and their de novo biosynthesis in yeast

Identification of the cytochrome P450s responsible for the biosynthesis of two types of aporphine alkaloids and their de novo biosynthesis in yeast

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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.

aporphine alkaloidsbiosynthesisCYP719CCYP80engineered yeast

Qishuang Li、Xiang Jiao、Xinyi Li、Wenlong Shi、Ying Ma、Xiangmei Tan、Jingyi Gan、Jimei Liu、Jian Yang、Jian Wang、Baolong Jin、Tong Chen、Ping Su、Yujun Zhao、Yifeng Zhang、Jinfu Tang、Guanghong Cui、Yun Chen、Juan Guo、Luqi Huang

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School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 211198,China

State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs,National Resource Center for Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China

Department of Life Sciences,Chalmers University of Technology,Gothenburg SE-41296,Sweden

State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing 100191,China

State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,The Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China

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2024

10.1111/jipb.13724

植物学报(英文版)
中国植物学会

植物学报(英文版)

CSTPCD
影响因子：0.921
ISSN：1672-9072
年,卷(期)：2024.66(8)