Divergent Protein Engineering of Transaminase for the Synthesis of Chiral Rivastigmine and Apremilast Precursors†
Langyu Tang
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
The authors contribute equally.
Search for more papers by this authorXinjie Yang
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
Longgang Institute of Zhejiang Sci-Tech University, Wenzhou, Zhejiang, 325802 China
The authors contribute equally.
Search for more papers by this authorNingning Sun
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
Search for more papers by this authorGuojiao Wu
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
Search for more papers by this authorYuzhou Wu
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
Search for more papers by this authorCorresponding Author
Fangrui Zhong
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
E-mail: [email protected]Search for more papers by this authorLangyu Tang
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
The authors contribute equally.
Search for more papers by this authorXinjie Yang
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
Longgang Institute of Zhejiang Sci-Tech University, Wenzhou, Zhejiang, 325802 China
The authors contribute equally.
Search for more papers by this authorNingning Sun
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
Search for more papers by this authorGuojiao Wu
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
Search for more papers by this authorYuzhou Wu
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
Search for more papers by this authorCorresponding Author
Fangrui Zhong
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
E-mail: [email protected]Search for more papers by this authorDedicated to the Special Issue of Emerging Investigators in 2024.
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 inexpensive α-methylbenzylamine as an amine donor and avoid the continuous acetone removal and costly LDH/GDH/NADH systems.
Supporting Information
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