研究人员发现了一种双功能细胞色素P450酶（紫杉烷氧杂环丁烷酶，TOT），它能催化紫杉醇氧杂环丁烷形成过程中的氧化重排，这代表了之前未知的氧杂环丁烷环形成酶机制。研究人员创建了一种基于紫杉素生物合成途径的筛选策略，并发现了负责紫杉烷C9位氧化的酶（T9αH）。最后，研究人员在烟草中人工重构了生产巴卡亭III的生物合成途径。
据悉，紫杉醇是一种著名的抗癌化合物。它的生物合成过程包括形成高官能度的二萜核心骨架（巴卡亭III），以及随后组装苯基异丝氨酸酰基侧链。尽管经过半个世纪的深入研究，巴卡亭III的完整生物合成途径仍然未知。
附：英文原文
Title: Characterization and heterologous reconstitution of Taxus biosynthetic enzymes leading to baccatin III
Author: 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
Issue&Volume: 2024-01-25
Abstract: 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. Here, we identified a bifunctional cytochrome P450 enzyme (Taxane oxetanase, TOT) that catalyzes an oxidative rearrangement in paclitaxel oxetane formation, representing 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 (T9αH). Finally, we artificially reconstituted a biosynthetic pathway for the production of baccatin III in tobacco.
DOI: adj3484
Source: https://www.science.org/doi/10.1126/science.adj3484