生物合成
红豆杉
酶
生物化学
环氧乙烷
紫杉烷
化学
甲戊酸途径
生物
立体化学
植物
遗传学
癌症
乳腺癌
高分子化学
作者
Bin Jiang,Lei Gao,Haijun Wang,Ya‐Ping Sun,Xiaolin Zhang,Kui Han,Shengchao Liu,Pengchen Ma,Qinggang Liao,Yue Wang,H Wang,Yugeng Liu,Ran Du,Torben Rogge,Wei Li,Yi Shang,K. N. Houk,Xingyao Xiong,Daoxin Xie,Sanwen Huang,Xiaoguang Lei,Jianbin Yan
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2024-02-09
卷期号:383 (6683): 622-629
被引量:8
标识
DOI:10.1126/science.adj3484
摘要
Paclitaxel is a well known anticancer compound. Its biosynthesis involves the formation of a highly functionalized diterpenoid core skeleton (baccatin III) and the subsequent assembly of a phenylisoserinoyl side chain. Despite intensive investigation for half a century, the complete biosynthetic pathway of baccatin III remains unknown. In this work, we identified a bifunctional cytochrome P450 enzyme [taxane oxetanase 1 (TOT1)] in Taxus mairei that catalyzes an oxidative rearrangement in paclitaxel oxetane formation, which represents a previously unknown enzyme mechanism for oxetane ring formation. We created a screening strategy based on the taxusin biosynthesis pathway and uncovered the enzyme responsible for the taxane oxidation of the C9 position (T9αH1). Finally, we artificially reconstituted a biosynthetic pathway for the production of baccatin III in tobacco.
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