Characterization and heterologous reconstitution of Taxus biosynthetic enzymes leading to baccatin III
文献类型: 外文期刊
作者: Bin Jiang;Lei Gao;Haijun Wang;Yaping Sun;Xiaolin Zhang;Han Ke;Shengchao Liu;Pengchen Ma;Qinggang Liao;Yue Wang;Huan Wang;Yugeng Liu;Ran Du;Torben Rogge;Wei Li;Yi Shang;K. N. Houk;Xingyao Xiong;Daoxin Xie;Sanwen Huang;Xiaoguang Lei;Jianbin Yan
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关键词: (1-1-1)
期刊名称: Science
ISSN: 0036-8075
年卷期: 2024 年 383 卷 6683 期
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收录情况: SCIE(2024版)
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 (T9aH1). Finally, we artificially reconstituted a biosynthetic pathway for the production of baccatin III in tobacco.
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