Divergent Protein Engineering of Transaminase for the Synthesis of Chiral Rivastigmine and Apremilast Precursors  

作　　者：Langyu Tang Xinjie Yang Ningning Sun Guojiao Wu Yuzhou Wu Fangrui Zhong 

机构地区：[1]Hubei Engineering Research Center for Biomaterials and Medical Protective Materials,Hubei Key Laboratory of Bioinorganic Chemistry&Materia Medica,School of Chemistry and Chemical Engineering,Huazhong University of Science and Technology,1037 Luoyu Road,Wuhan,Hubei 430074,China [2]Longgang Institute of Zhejiang Sci-Tech University,Wenzhou,Zhejiang 325802,China [3]Shenzhen Huazhong University of Science and Technology Research Institute,Shenzhen,Guangdong 518000,China

出　　处：《Chinese Journal of Chemistry》2024年第19期2335-2340,共6页中国化学（英文版）

基　　金：the National Key R&D Program of China(No.2021YFF1200203 to G.W.and 2018YFA0903500 to F.Z.);Hubei Provincial Key R&D program(2021BAA168 to Y.W.);Shen-Zhen Science and Technology Program(JCYJ20220530160805011 to F.Z.);the interdisciplinary research program of Huazhong University of Science and Technology(HUST)(2023JCYJ001 to F.Z.);the China Postdoctoral Science Foundation(2023M741259 to X.Y.)for financial supports.

摘　　要：Comprehensive Summary The implementation of divergent protein engineering on the natural transaminase Vf-ω-TA led to the development of two effective mutants(M2 and M8),enabling the enzymatic synthesis of chiral amine precursors of Rivastigmine and Apremilast,respectively.The evolution of the enzymes was guided by crystal structures and a focused mutagenesis strategy,allowing them to effectively address the challenging ketone substrates with significant steric hindrance.Under the optimized reaction parameters,transamination proceeded smoothly in good conversions and with perfect stereochemical control(>99%ee).These processes utilize inexpensiveα-methylbenzylamine as an amine donor and avoid the continuous acetone removal and costly LDH/GDH/NADH systems.

关 键 词：Asymmetric catalysis Chiral amine Protein engineering Directed evolution BIOCATALYSIS TRANSAMINASE ENANTIOSELECTIVITY Syntheticmethods AMINATION Enzymes 

分 类 号：O62[理学—有机化学]