非原生分子内激素循环,由B12依赖酶催化
Jianbin Li1, Amardeep Kumar1, Jared C Lewis1
1Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Angewandte Chemie (International ed. in English)
|October 24, 2023
概括
研究人员重新使用了一种依赖维生素B12的酶CarH,用于新的激素循环反应. 工程化酶CarH*有效地形成乳酸和独特的螺旋环,扩大生物催化剂的应用.
科学领域:
- 生物催化剂是一种生物催化剂.
- 酶工程是什么? 酶工程是什么?
- 有机合成 有机合成
背景情况:
- 维生素B12 (科巴胺) 和其衍生物具有独特的反应性.
- 目前,依赖于B12的酶在生物催化剂中未得到充分利用.
- 转录因子为酶工程提供了潜在的蛋白质支架.
研究的目的:
- 为了重新利用B12依赖的转录因子CarH用于非原生激素循环反应.
- 设计一种变体,CarH*,对B12催化转换具有增强的反应性和选择性.
- 探索工程B12依赖酶在形成复杂循环结构中的合成实用性.
主要方法:
- 将依赖于B12的转录因子CarH转化为CarH*.
- 使用 CarH* 催化激素循环反应.
- 机制研究以阐明反应途径和辅因子控制.
主要成果:
- CarH* 通过氧化还原中性或还原环闭成功催化了玛乳酸和三角乳酸的形成.
- 与自由B12辅因子相比,工程酶显示出增强的反应性和选择性.
- 通过悬挂的 dearomatization,CarH* 实现了不寻常的螺旋循环,产生双循环的1,3-dienes.
- 证明了一种新的合成路径到1,3-二烯,与现有的1,4-二烯方法不同.
结论:
- 蛋白质支架对于控制维生素B12辅因子的反应性至关重要.
- 重新设计的B12依赖酶,如CarH*,显著扩大了合成生物催化剂工具箱.
- 这项工作突出了设计B12依赖酶用于新型化学转换的潜力.
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