Direct reductive amination of ketones with amines by reductive aminases
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)...
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| Auteurs principaux: | , , , , , |
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| Format: | article |
| Langue: | EN |
| Publié: |
KeAi Communications Co. Ltd.
2021
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| Accès en ligne: | https://doaj.org/article/bcbca17f03544cf0868c9195bde2c22d |
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| Résumé: | 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. |
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