A growth selection system for the directed evolution of amine-forming or converting enzymes

Shuke Wu (), Chao Xiang, Yi Zhou, Mohammad Saiful Hasan Khan, Weidong Liu, Christian G. Feiler, Ren Wei, Gert Weber, Matthias Höhne and Uwe T. Bornscheuer ()
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Shuke Wu: University of Greifswald
Chao Xiang: University of Greifswald
Yi Zhou: Huazhong Agricultural University
Mohammad Saiful Hasan Khan: University of Greifswald
Weidong Liu: University of Greifswald
Christian G. Feiler: Helmholtz-Zentrum Berlin für Materialien und Energie
Ren Wei: University of Greifswald
Gert Weber: Helmholtz-Zentrum Berlin für Materialien und Energie
Matthias Höhne: University of Greifswald
Uwe T. Bornscheuer: University of Greifswald

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract Fast screening of enzyme variants is crucial for tailoring biocatalysts for the asymmetric synthesis of non-natural chiral chemicals, such as amines. However, most existing screening methods either are limited by the throughput or require specialized equipment. Herein, we report a simple, high-throughput, low-equipment dependent, and generally applicable growth selection system for engineering amine-forming or converting enzymes and apply it to improve biocatalysts belonging to three different enzyme classes. This results in (i) an amine transaminase variant with 110-fold increased specific activity for the asymmetric synthesis of the chiral amine intermediate of Linagliptin; (ii) a 270-fold improved monoamine oxidase to prepare the chiral amine intermediate of Cinacalcet by deracemization; and (iii) an ammonia lyase variant with a 26-fold increased activity in the asymmetric synthesis of a non-natural amino acid. Our growth selection system is adaptable to different enzyme classes, varying levels of enzyme activities, and thus a flexible tool for various stages of an engineering campaign.

Date: 2022
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DOI: 10.1038/s41467-022-35228-y

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