Divergent Protein Engineering of Transaminase for the Synthesis of Chiral Rivastimine and Apremilast Precuarsors

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外文摘要：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 pro-ceeded 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.

外文关键词：

Asymmetric catalysisChiral amineProtein engineeringDirected evolutionBiocatalysisTransaminaseEnantioselectivitySynthetic methodsAminationEnzymes

作者：

Langyu Tang、Xinjie Yang、Ningning Sun、Guojiao Wu、Yuzhou Wu、Fangrui Zhong

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作者单位：

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

Shenzhen Huazhong University of Science and Technology Research Institute,Shenzhen,Guangdong 518000,China

Longgang Institute of Zhejiang Sci-Tech University,Wenzhou,Zhejiang 325802,China

出版年：

2024

DOI：

10.1002/cjoc.202400351

中国化学(英文版)

中国化学会上海有机化学研究所

中国化学(英文版)

CSTPCD

影响因子：0.848

ISSN：1001-604X

年,卷(期)：2024.42(19)