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

Cephalotaxines harbor great medical potential, but their natural source, the endemic conifer 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...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2023-01, Vol.120 (1), p.e2209339120-e2209339120
Main Authors: Qiao, Fei, He, Yuedong, Zhang, Yuhao, Jiang, Xuefei, Cong, Hanqing, Wang, Zhiming, Sun, Huapeng, Xiao, Yibei, Zhao, Yucheng, Nick, Peter
Format: Article
Language:English
Subjects:
Alkaloids
Benzylisoquinolines
Biodiversity
Biological Sciences
Biosynthesis
Biotechnology
Cephalotaxus - genetics
Cephalotaxus hainanensis
Condensates
Conifers
Preservation
Transcriptomes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cephalotaxines harbor great medical potential, but their natural source, the endemic conifer 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 transcriptome mining of  to infer the biosynthesis for PIA precursor. We identify a novel protein, PSS, 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 DBR 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2209339120