AUTHOR=Zhang Kai , He Yuanzhi , Zhu Jiawei , Zhang Qi , Tang Luyao , Cui Li , Feng Yan 

TITLE=Engineering of Reductive Aminases for Asymmetric Synthesis of Enantiopure Rasagiline

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2021.798147

DOI=10.3389/fbioe.2021.798147

ISSN=2296-4185

ABSTRACT=<p>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 <italic>Aspergillus calidoustus</italic> (<italic>Ac</italic>RedAm) and bacteria (<italic>Ba</italic>RedAm) 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 (<italic>R</italic>)-rasagiline, we engineered <italic>Ac</italic>RedAm through rational design to obtain highly stereoselective mutants. The best mutant Q237A from <italic>Ac</italic>RedAm could synthesize (<italic>R</italic>)-rasagiline with &gt;99% enantiomeric excess with moderate conversion. The features of <italic>Ac</italic>RedAm and <italic>Ba</italic>RedAm highlight their potential for further study and expand the biocatalytic toolbox for industrial applications.</p>