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一种细胞染色体P450酶催化了在帕克利塔塞尔生物合成中的氧化环形成

Changkang Li¹, Xinxin Yin¹, Shuai Wang^1,2

¹State Key Laboratory of Bioactive Substance and Function of Natural Medicines, CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs, NHC Key Laboratory of Biosynthesis of Natural Products, and Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Angewandte Chemie (International ed. in English)

|May 7, 2024

概括

氧乙合成酶 (TmCYP1) 催化氧乙环的形成在taxoids. C5-O-乙基对氧乙环结构至关重要,有助于了解帕克利塔克塞尔生物合成.

科学领域:

生物化学生物化学
酶学是一种酶学.
自然产品生物合成自然产品生物合成

背景情况:

四环毒素是复杂的天然产品,具有重要的制药应用.
帕克利塔克塞尔生物合成涉及复杂的酶步骤,包括形成独特的结构图案.
细胞染色体P450酶在自然产品的新陈代谢中发挥着不同的作用.

研究的目的:

为了功能性地描述一种新型的细胞染色体P450酶的氧乙合成酶 (TmCYP1).
为了阐明四环氧化物中氧化环形成的酶机制.
了解TmCYP1在帕克利塔塞尔生物合成途径中的作用.

主要方法:

在Nicotiana benthamiana中TmCYP1的暂时表达.
用特定的化物衍生物进行基质养实验.
同位素标记研究 (2H和18O) 和密度函数理论计算.

主要成果:

TmCYP1有效地催化了从六氧化基质中形成一个氧化环.
在使用5-脱乙基化基质时,4β,20-环氧化衍生物被确定为主要或唯一产品.
发现C5-O-乙基对于氧乙环的形成是必不可少的,但对于环氧化物的形成不是.

结论:

TmCYP1 是一个关键酶,在帕克利塔克塞尔生物合成过程中形成氧化环.
反应机制涉及分子内氧化-乙基重组,可能通过协调的过程.
这些发现提供了对构建taxoids中oxetane部分的酶策略的关键见解.

关键词:

生物合成生物合成细胞染色体P450的使用.同位素标签的标签自然产品是天然产品.氧乙氧乙氧乙氧乙

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