高氧化四环核骨架的生物合成Taxol的高氧化四环核骨架
Chengshuai Yang1, Yan Wang1, Zhen Su1,2
1Key Laboratories of Plant Design and Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.
Nature communications
|March 16, 2024
概括
研究人员阐明了抗癌药物Taxol (paclitaxel) 生物合成的关键步骤,确定了新的酶和反应机制. 这项工作促进了我们对Taxol生产途径的理解,为潜在的治疗开发提供了帮助.
科学领域:
- 生物化学 生物化学
- 有机化学 有机化学
- 分子生物学分子生物学
背景情况:
- 塔克索 (帕克利塔塞尔) 是一种关键的抗癌药物,向微管体动力学.
- 虽然已知许多Taxol生物合成中的酶,但从二氧化塔克索酸到核心骨架的确切途径尚不清楚.
研究的目的:
- 阐明导致Taxol四环核的逐步生物合成反应.
- 为了确定参与Taxol生物合成的新型酶和机制.
- 为了在工程酵母中实现TAXOL的完整生物合成.
主要方法:
- 酶表征和活性测定.
- 确认基化反应的顺序.
- 标识一个高体9α-基酶和CYP725A55.55.
- 一个乙转移酶的识别.
- 酵母的代谢工程用于Taxol生物合成.
主要成果:
- 证实了第二和第三个基化步骤的临界顺序.
- 确定了一种新型的高体9α-基酶和CYP725A55 (参与氧乙烯 Ester形成).
- 确定了一种负责C7-OAc形成的乙转移酶.
- 阐明了1β-脱基巴丁VI的途径.
- 在来自 taxa-4(20),11(12) -diene-5α-ol 的工程酵母中实现了完整的taxol生物合成.
结论:
- 这项研究通过阐明关键的酶步骤和反应机制,大大提高了对Taxol生物合成的理解.
- 新型酶的鉴定和成功的工程酵母菌株为未来的Taxol生产策略提供了基础.
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