Direct reductive amination of ketones with amines by reductive aminases

Bo-Bo Li; Jing Zhang; Fei-Fei Chen; Qi Chen; Jian-He Xu; Gao-Wei Zheng

Green Synthesis and Catalysis (Nov 2021)

Direct reductive amination of ketones with amines by reductive aminases

Bo-Bo Li,
Jing Zhang,
Fei-Fei Chen,
Qi Chen,
Jian-He Xu,
Gao-Wei Zheng

Affiliations

Bo-Bo Li: State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing, East China University of Science and Technology, Shanghai 200237, China
Jing Zhang: State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing, East China University of Science and Technology, Shanghai 200237, China
Fei-Fei Chen: State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing, East China University of Science and Technology, Shanghai 200237, China
Qi Chen: State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing, East China University of Science and Technology, Shanghai 200237, China
Jian-He Xu: State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing, East China University of Science and Technology, Shanghai 200237, China; Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai 200237, China
Gao-Wei Zheng: State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing, East China University of Science and Technology, Shanghai 200237, China; Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai 200237, China; Corresponding author. State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing, East China University of Science and Technology, Shanghai 200237, China.

Journal volume & issue: Vol. 2, no. 4
pp. 345 – 349

Abstract

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Direct reductive amination of ketones by reductive aminases (RedAms) is a promising method for the synthesis of primary, secondary and tertiary amines. In this work, five naturally occurring RedAms possessing reductive amination activity were identified using a structure-guided genome mining (SGGM) approach, which was based on highly conserved substrate binding and catalysis motif alignment. This RedAm toolbox facilitated the reductive amination of cyclohexanone and 4-fluoropropiophenone with various amine nucleophiles. In a preparative biotransformation (100 mg) with low stoichiometric ammonia donor and low catalyst loading, and three types of N-alkylcyclohexylamine were efficiently synthesized with a space-time yield up to 64.2 g L−1 d−1, demonstrating the potential of the RedAm enzymes as a biocatalyst toolbox for the synthesis of primary and secondary amines. Additionally, through protein engineering, the W205F variant of KfRedAm from Kribbella flavida was obtained with a 2-fold increased catalytic efficiency (kcat/Km), and the general applicability of the variant was verified, providing useful guidance for further evolution of RedAms within this family.

Published in Green Synthesis and Catalysis

ISSN: 2666-5549 (Online)
Publisher: KeAi Communications Co. Ltd.
Country of publisher: China
LCC subjects: Technology: Chemical technology; Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.keaipublishing.com/en/journals/green-synthesis-and-catalysis/

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