铜复合体与基于蛋白质的N-捐赠体作为cis-Selective新生的环旋酶
Nobutaka Fujieda1, Atsuki Matsuo2, Shinobu Itoh2
1Department of Applied Biological Chemistry, Graduate School of Agriculture, Osaka Metropolitan University, 1-1 Gakuen-cho, Naka-ku, Sakai-shi, Osaka, 599-8531, Japan.
Chemistry (Weinheim an der Bergstrasse, Germany)
|September 11, 2024
概括
研究人员设计了来自TM1459 cupin超级家族的基于蛋白质的金属配体,以催化 cis-选择性循环化. 铜复合物表现出高的二选择性和选择性,提高了催化效率.
科学领域:
- 生物催化剂是一种生物催化剂.
- 蛋白质工程是指蛋白质的工程.
- 有机金属化学 有机金属化学
背景情况:
- 蛋白质工程为设计新型催化剂提供了一种强大的方法.
- 库宾蛋白为开发金属酶提供了一个多功能支架.
- 循环化反应在有机合成中至关重要.
研究的目的:
- 为了设计基于蛋白质的金属连接物用于 cis-选择性环.
- 为了利用TM1459 cupin蛋白超级家族作为催化剂开发的支架.
- 通过蛋白质修饰来增强催化活性和选择性.
主要方法:
- TM1459蛋白的位点定向突变发生,以引入金属结合位点.
- 复合铜离子到工程蛋白质突变体.
- 在循环化反应中对铜-蛋白质复合物的催化评估.
- 优化二次协调球体残留物以提高选择性.
主要成果:
- 具有3-His金属结合部位的TM1459突变物有效催化了具有高二选择性的环.
- 铜复合物与 styrene 和 ethyl diazoacetate 呈现出极好的催化性能.
- 进一步的突变增强了 cis-选择性,达到 80:20 的 cis:trans 比率,使用t-butyl diazoacetate.
- 通过优化蛋白质连接体,实现了高的酶选择性 (90% ee).
结论:
- 基于蛋白质的金属连接物可以成功地被设计为选择性催化转换.
- TM1459 cupin 脚手架适用于开发新型金属酶.
- 这项工作为设计用于循环和其它有机反应的高度选择性生物催化剂提供了基础.
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