Enabling sustainable supply of the essential cancer medicines etoposide and teniposide in yeast
Journal article, 2026
Lignans constitute a diverse family of plant metabolites with therapeutic potential. Among them, podophyllotoxin-type aryltetralin lignans serve as precursors for etoposide and teniposide. Etoposide is an essential anticancer medicine approved for first-line treatment of small cell lung cancer, whereas teniposide is used for treatment of leukemia and some brain tumors. Currently, these drugs depend on extraction of precursors from the endangered plant Sinopodophyllum hexandrum, followed by chemical transformations. By identifying key glycosyltransferases and executing more than 60 genetic edits involving 45 heterologous enzymes, the complex biosynthetic pathway of podophyllotoxin-type lignans was reconstructed in yeast. In this study, we established a chemoenzymatic route that streamlines the synthesis of etoposide and teniposide through a single chemical step from biosynthetic precursor 4'-demethyl-epipodophyllotoxin-4-O-glucoside, which enables a secure supply chain of these essential medicines.
Author
Siyu Shen
Capital Medical University
China Academy of Chinese Medical Sciences
Xue Hu
Capital Medical University
Dan Li
Capital Medical University
Y. R. Tong
Capital Medical University
Yunpeng Lv
Capital Medical University
Zhenjiang Tian
Capital Medical University
Jiadian Wang
Capital Medical University
Hao Tang
China Academy of Chinese Medical Sciences
Yapeng Wang
China Academy of Chinese Medical Sciences
Lan Kang
China Academy of Chinese Medical Sciences
Jens B Nielsen
Chalmers, Life Sciences, Systems and Synthetic Biology
BII Holdings A/S
Luqi Huang
China Academy of Chinese Medical Sciences
Yating Hu
China Academy of Chinese Medical Sciences
Capital Medical University
Science
00368075 (ISSN) 10959203 (eISSN)
Vol. 393 6810 aef5438-Subject Categories (SSIF 2025)
Chemical Sciences
DOI
10.1126/science.aef5438
PubMed
42531388