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Engineering of Reductive Aminases for Asymmetric Synthesis of Enantiopure Rasagiline.

ABSTRACT: Reductive aminases (RedAms) for the stereoselective amination of ketones represent an environmentally benign and economically viable alternative to transition metal-catalyzed asymmetric chemical synthesis. Here, we report two RedAms from Aspergillus calidoustus (AcRedAm) and bacteria (BaRedAm) with NADPH-dependent features. The enzymes can synthesize a set of secondary amines using a broad range of ketone and amine substrates with up to 97% conversion. To synthesize the pharmaceutical ingredient (R)-rasagiline, we engineered AcRedAm through rational design to obtain highly stereoselective mutants. The best mutant Q237A from AcRedAm could synthesize (R)-rasagiline with >99% enantiomeric excess with moderate conversion. The features of AcRedAm and BaRedAm highlight their potential for further study and expand the biocatalytic toolbox for industrial applications.

SUBMITTER: Zhang K

PROVIDER: S-EPMC8727753 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Engineering of Reductive Aminases for Asymmetric Synthesis of Enantiopure Rasagiline.

Zhang Kai K He Yuanzhi Y Zhu Jiawei J Zhang Qi Q Tang Luyao L Cui Li L Feng Yan Y

Frontiers in bioengineering and biotechnology 20211222

Reductive aminases (RedAms) for the stereoselective amination of ketones represent an environmentally benign and economically viable alternative to transition metal-catalyzed asymmetric chemical synthesis. Here, we report two RedAms from Aspergillus calidoustus (AcRedAm) and bacteria (BaRedAm) with NADPH-dependent features. The enzymes can synthesize a set of secondary amines using a broad range of ketone and amine substrates with up to 97% conversion. To synthesize the phar ...[more]

PMID: 35004654

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