由酶控制的立体选择性基因循环转化到由metalloredox生物催化剂启动的基
Wenzhen Fu1, Natalia M Neris1, Yue Fu2
1Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, USA.
Nature catalysis
|February 26, 2024
概括
这项研究引入了一种新的生物催化方法,使用工程化细胞染色体P450进行不对称的基因循环. 这些酶实现了高立体控制,为复杂分子合成提供了多功能平台.
科学领域:
- 生物催化剂是一种生物催化剂.
- 不对称的催化剂.
- 金属氧化物化学 化学
背景情况:
- 在自由基反应中实现高立体控制是合成化学的一个重大挑战.
- 自然的P450细胞染色体通常通过不同的机制运作,而不是激进循环.
研究的目的:
- 开发一种新的metalloredox生物催化策略,用于使用工程化细胞染色体P450.0.进行不对称的基因循环.
- 探索定向进化的潜力,以定制P450酶用于激素催化.
主要方法:
- 通过定向进化重新利用自然的P450细胞染色体.
- 利用一种非自然的电子转移机制来产生激素.
- 使用计算研究来阐明反应机制.
主要成果:
- 工程P450变体 (P450arc1,P450arc2) 实现了具有高周转数 (高达12,000) 的racemic基质的enantioconvergent基因循环.
- 一种不同的变体 (P450arc3) 能够有效地分辨具有高S因子 (18) 的种族化物基质的动态分辨率.
- 计算分析表明,一种合质子电子转移 (PCET) 机制涉及碳酸盐作为潜在的基质催化剂.
结论:
- 工程P450酶提供了一个可调和和有效的平台,用于不对称的基因循环.
- 这种金属酶家族提供了一个强大的新工具,用于控制催化剂中的激素中间体.
- 这些发现为生物催化在复杂有机合成中的更广泛应用开辟了道路.
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