Elucidation of the 1-phenethylisoquinoline pathway from an endemic conifer Cephalotaxus hainanensis

文献类型： 外文期刊

第一作者： Qiao, Fei

作者： Qiao, Fei;He, Yuedong;Cong, Hanqing;Sun, Huapeng;Qiao, Fei;He, Yuedong;Cong, Hanqing;Sun, Huapeng;He, Yuedong;Zhang, Yuhao;Zhao, Yucheng;Jiang, Xuefei;Wang, Zhiming;Jiang, Xuefei;Wang, Zhiming;Xiao, Yibei;Xiao, Yibei;Nick, Peter

作者机构：

关键词： C; hainanensis; phenylethylisoquinoline; 1-phenethylisoquinoline; ChPSS

期刊名称：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA （ 影响因子：11.1； 五年影响因子：12.0 ）

ISSN： 0027-8424

年卷期： 2022 年 120 卷 1 期

页码：

收录情况： SCI

摘要： Cephalotaxines harbor great medical potential, but their natural source, the endemic conifer Cephalotaxus is highly endangered, creating a conflict between biotechnological valorization and preservation of biodiversity. Here, we construct the whole biosynthetic pathway to the 1-phenethylisoquinoline scaffold, as first committed compound for phenylethylisoquinoline alkaloids (PIAs), combining metabolic modeling, and transcrip-tome mining of Cephalotaxus hainanensis to infer the biosynthesis for PIA precursor. We identify a novel protein, ChPSS, driving the Pictet-Spengler condensation and show that this enzyme represents the branching point where PIA biosynthesis diverges from the concurrent benzylisoquinoline-alkaloids pathway. We also pinpoint ChDBR as crucial step to form 4-hydroxydihydrocinnamaldehyde diverging from lignin biosynthesis. The elucidation of the early PIA pathway represents an important step toward microbe-based production of these pharmaceutically important alkaloids resolving the conflict between biotechnology and preservation of biodiversity.Significance1-phenethylisoquinoline is the common scaffold of the phenylethylisoquinoline alkaloids (PIAs) that are relevant as anti-tumor compounds. The endemic conifer Cephalotaxus hainanensis produces the PIA homoharringtonine, highly potent against leukemia. The PIA scaffold is formed by a Pictet-Spengler condensation from dopamine and 4-HDCA, but the respective enzyme has remained elusive. Using a novel strategy, we identify this enzyme, construct the entire biosynthetic pathway leading to the precursors, and validate the implications of the identified enzymes by measuring their metabolic activities in vitro.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序