文献类型： 外文期刊

作者： Qiao, Fei ¹ ; He, Yuedong ¹ ; Zhang, Yuhao ⁴ ; Jiang, Xuefei ⁵ ; Cong, Hanqing ¹ ; Wang, Zhiming ⁵ ; Sun, Huapeng ¹ ; Xiao, Yibei ⁷ ; Zhao, Yucheng ⁴ ; Nick, Peter ⁹ ;

作者机构： 1.Chinese Acad Trop Agr Sci, Minist Agr, Key Lab Crop Gene Resources & Germplasm Enhancemen, Haikou 571101, Peoples R China

2.Chinese Acad Trop Agr Sci, Trop Crops Genet Resources Inst, Haikou 571101, Peoples R China

3.Hunan Agr Univ, Coll Hort, Changsha 410128, Peoples R China

4.China Pharmaceut Univ, Sch Tradit Chinese Pharm, Dept Resources Sci Tradit Chinese Med, Nanjing 210009, Peoples R China

5.Hainan Univ, Coll Hort, Hainan Key Lab Sustainable Utilizat Trop Bioresour, Haikou 570228, Peoples R China

6.Hainan Univ, Coll Hort, Key Lab Qual Regulat Trop Hort Plants Hainan Prov, Haikou 570228, Peoples R China

7.China Pharmaceut Univ, Sch Pharm, Dept Pharmacol, Nanjing 210009, Peoples R China

8.China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Peoples R China

9.Karlsruhe Inst Technol, Bot Inst, Mol Cell Biol, D-76131 Karlsruhe, Germany

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.