Characterization and heterologous reconstitution of Taxus biosynthetic enzymes leading to baccatin III

文献类型： 外文期刊

第一作者： Jiang, Bin

作者： Jiang, Bin;Sun, Yaping;Zhang, Xiaolin;Liu, Shengchao;Liao, Qinggang;Wang, Yue;Wang, Huan;Liu, Yugeng;Du, Ran;Li, Wei;Xiong, Xingyao;Huang, Sanwen;Yan, Jianbin;Gao, Lei;Wang, Haijun;Ke, Han;Lei, Xiaoguang;Sun, Yaping;Ma, Pengchen;Rogge, Torben;Houk, K. N.;Shang, Yi;Xie, Daoxin;Lei, Xiaoguang

作者机构：

期刊名称：SCIENCE （ 影响因子：56.9； 五年影响因子：54.5 ）

ISSN： 0036-8075

年卷期： 2024 年 383 卷 6681 期

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收录情况： SCI

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 (T9 alpha H1). Finally, we artificially reconstituted a biosynthetic pathway for the production of baccatin III in tobacco.

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