立体选择性
化学
部分
亚胺
选择性
立体化学
合理设计
突变
组合化学
酮
有机化学
生物化学
突变
纳米技术
催化作用
基因
材料科学
作者
Jun Zhang,Yaqing Ma,Fukang Zhu,Jianchun Bao,Qingping Wu,Shiqiang Gao,Chengsen Cui
出处
期刊:Chemical Science
[The Royal Society of Chemistry]
日期:2023-01-01
卷期号:14 (16): 4265-4272
被引量:9
摘要
In this study, engineered imine reductases (IREDs) of IRED M5, originally from Actinoalloteichus hymeniacidonis, were obtained through structure-guided semi-rational design. By focusing on mutagenesis of the residues that directly interact with the ketone donor moiety, we identified two residues W234 and F260, playing essential roles in enhancing and reversing the stereoselectivity, respectively. Moreover, two completely enantio-complementary variants S241L/F260N (R-selectivity up to 99%) and I149D/W234I (S-selectivity up to 99%) were achieved. Both variants showed excellent stereoselectivity toward the tested substrates, offering valuable biocatalysts for synthesizing pyrrolidinamines. Its application was demonstrated in a short synthesis of the key intermediates of potential drug molecules leniolisib and JAK1 inhibitor 4, from cheap and commercially available pro-chiral N-Boc-piperidone 1 (2 and 3 steps, respectively).
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