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

Qiao, Fei; He, Yuedong; Zhang, Yuhao; Jiang, Xuefei; Cong, Hanqing; Wang, Zhiming; Sun, Huapeng ; Xiao, Yibei ; Zhao, Yucheng ; Nick, Peter 1
1 Joseph Gottlieb Kölreuter Institut für Pflanzenwissenschaften (JKIP), Karlsruher Institut für Technologie (KIT)

Abstract:

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 transcriptome 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.


Verlagsausgabe §
DOI: 10.5445/IR/1000154651
Veröffentlicht am 19.01.2023
Originalveröffentlichung
DOI: 10.1073/pnas.2209339120
Scopus
Zitationen: 5
Web of Science
Zitationen: 2
Dimensions
Zitationen: 4
Cover der Publikation
Zugehörige Institution(en) am KIT Joseph Gottlieb Kölreuter Institut für Pflanzenwissenschaften (JKIP)
Publikationstyp Zeitschriftenaufsatz
Publikationsdatum 03.01.2023
Sprache Englisch
Identifikator ISSN: 0027-8424, 1091-6490
KITopen-ID: 1000154651
Erschienen in Proceedings of the National Academy of Sciences of the United States of America
Verlag National Academy of Sciences
Band 120
Heft 1
Seiten Art.-Nr.:e2209339120
Vorab online veröffentlicht am 28.12.2022
Schlagwörter C. hainanensis, phenylethylisoquinoline alkaloids, 1-phenethylisoquinoline, ChPSS
Nachgewiesen in Dimensions
Web of Science
Scopus
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