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Semirational Protein Engineering of a Decarboxylative Aldolase for the Regiodivergent and Stereodivergent Synthesis of Cyclic Imino Acids

文献类型：期刊论文

作者Lan, Yuqiu1,5; Zhang, Chenghua3; Tang, Chunping4; Ye, Yang4; Zhang, Rui1; Sheng, Xiang2,5,6; Liao, Cangsong1,5
刊名ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
出版日期2025-03-10
卷号64期号:11页码:7
关键词protein engineering biocatalysis aldolase regioselectivity cyclic imino acids
DOI10.1002/anie.202500080
英文摘要Aldolases are powerful C-C bond-forming enzymes for asymmetric organic synthesis because of their supreme stereoselectivity, compatibility with diverse electrophiles and nucleophiles, and promising scalability. Stereodivergent engineering of aldolases to tune the selectivity for the synthesis of stereoisomers of chiral molecules is highly desirable but has rarely been reported. Herein we report the semirational engineering of the decarboxylative aldolase UstD with a focused rational iterative site-specific mutagenesis (FRISM) strategy to perform a C-C bond-forming reaction with dione electrophiles. The variant obtained from a small mutant library showed divergent regioselectivity and diastereoselectivity compared to the wild-type enzyme, resulting in the production of 30 cyclic imino acids with stereocenters at the alpha and gamma positions. Molecular dynamics simulation and kinetic data revealed the basis of selectivity.
WOS关键词THREONINE ALDOLASE
资助项目National Key Research and Development Program of China ; National Natural Science Foundation of China (NSFC)[22071259] ; National Natural Science Foundation of China (NSFC)[22307130] ; National Natural Science Foundation of China (NSFC)[22103095] ; Key-Area Research and Development Program of Guangdong Province[2020B0303070002] ; Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences ; [2021YFA0911500]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001440744200043
出版者WILEY-V C H VERLAG GMBH
源URL[http://119.78.100.183/handle/2S10ELR8/321096]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Zhang, Rui; Sheng, Xiang; Liao, Cangsong
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Key Lab Engn Biol Low Carbon Mfg, Tianjin 300308, Peoples R China
3.North Sichuan Med Coll, Sch Pharm, Nanchong 637100, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
6.Natl Ctr Technol Innovat Synthet Biol, Tianjin 300308, Peoples R China
推荐引用方式
GB/T 7714		 Lan, Yuqiu,Zhang, Chenghua,Tang, Chunping,et al. Semirational Protein Engineering of a Decarboxylative Aldolase for the Regiodivergent and Stereodivergent Synthesis of Cyclic Imino Acids[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2025,64(11):7.
APA Lan, Yuqiu.,Zhang, Chenghua.,Tang, Chunping.,Ye, Yang.,Zhang, Rui.,...&Liao, Cangsong.(2025).Semirational Protein Engineering of a Decarboxylative Aldolase for the Regiodivergent and Stereodivergent Synthesis of Cyclic Imino Acids.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,64(11),7.
MLA Lan, Yuqiu,et al."Semirational Protein Engineering of a Decarboxylative Aldolase for the Regiodivergent and Stereodivergent Synthesis of Cyclic Imino Acids".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 64.11(2025):7.

入库方式： OAI收割

来源：上海药物研究所

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