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含氧和含硫异环的氧化,由细胞P450酶

Matthew N Podgorski¹, Angus B Keto², Tom Coleman¹

¹Department of Chemistry, University of Adelaide, Adelaide, SA, 5005, Australia.

Chemistry (Weinheim an der Bergstrasse, Germany)

|June 20, 2023

概括

细菌酶CYP199A4优先对含烯的化合物进行硫化,形成二元代谢产物. 这种细胞染色体P450酶更喜欢硫氧化而不是芳香氧化,为异环代谢提供了洞察力.

科学领域:

生物化学生物化学
酶学是一种酶学.
有机化学有机化学

背景情况:

细胞染色体P450 (CYP) 酶对于代谢各种分子至关重要.
异环和芳香功能组在药品和天然产品中很常见.
了解CYP酶活性是药物代谢和异生物分解的关键.

研究的目的:

通过细菌酶CYP199A4.4对含硫和含氧异环化合物的氧化进行研究.
为了阐明代谢途径和产品形成的thiophene和 furan 基底.
为了确定CYP199A4介导氧化过程的区域选择性和立体选择性.

主要方法:

进行X射线晶体学以确定酶基质相互作用.
生物化学测试用于测量酶活性和产品形成.
计算计算以预测反应机制和产品分布.

主要成果:

通过硫氧化,CYP199A4选择性氧化了4---2-yl) 酸和4---3-yl) 酸,形成二元烯氧化物.
尽管芳香碳与血红素相近,但硫化被青,这表明人们更喜欢氧化.
氧化4 - - furan - 2 - - 酸通过一个γ-keto-α,β-不和阿尔德海德中间体产生了4 - - - 4 - - - - - - - - - - - - 酸.

结论:

CYP199A4对 thiophene 环的硫化有强烈的偏好,导致独特的二次代谢产物.
该酶的活性提供了对异环化合物代谢的详细见解.
结合结构,生化和计算数据,提高了对细胞染色体P450反应机制的理解.

关键词:

在X射线晶体学.细胞染色体P450酶中的一种.酶机制的酶机制是什么不同周期的异环环.金属酶是一种金属酶.

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