替代性血结合指导工程化P450催化碳转移反应中的活性和选择性
Kai Chen1, Shuo-Qing Zhang2, Oliver F Brandenberg1
1Division of Chemistry and Chemical Engineering 210-41 , California Institute of Technology , Pasadena , California 91125 , United States.
Journal of the American Chemical Society
|October 30, 2018
概括
工程P450酶催化了碳转移反应. 修改单个残留物可以选择性烯酸环或S-H键插入,从而产生有价值的乳化合物.
科学领域:
- 生物催化和酶工程
- 有机化学
- 计算化学
背景情况:
- 细胞P450酶是多功能生物催化剂.
- 碳转移反应在有机合成中至关重要.
- 控制新化学转换的酶选择性仍然是一个挑战.
研究的目的:
- 开发一种生物催化平台,用于使用工程化P450细胞染色体的碳转移反应.
- 研究血结合残留在控制酶反应性和选择性的作用.
- 为了使各种螺旋[2.4]乳和α-thio-γ-乳的合成.
主要方法:
- 使用基于乳的碳素前体的细胞P450酶的工程.
- 血结合残留物 (氨酸或氨酸) 的修改.
- 用于评估酶活性,效率和立体选择性的催化试验.
- 计算研究以阐明反应机制.
主要成果:
- 获得了两种工程酶:一种用于烯酸环化 (Ser),另一种用于S-H键插入 (Cys).
- 这两种酶都表现出高的催化效率和立体选择性.
- 可以轻松获得结构多样化的螺旋[2.4]乳和α-thio-γ-乳.
- 计算分析揭示了S-H插入的机制以及轴联体对反应性的影响.
结论:
- 工程P450酶为碳转移反应提供了强大的平台.
- 通过改变血结合残留物,可以精确调节酶选择性.
- 这项工作扩大了血蛋白的合成效用,并为设计新的生物催化剂提供了策略.
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