Redox cascade reaction for kinetic resolution of racemic α-methylbenzylamine and biosynthesis of α-phenylethanol

• Published in: Applied microbiology and biotechnology Vol. 107; no. 1; pp. 125 - 135
• Main Authors: Liu, Jinbin, Wang, Minyang, Liang, Chen, Deng, Huaxiang, Yu, Xiaohong
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 2023; Springer Nature B.V
• Subjects: Acetophenone; Aldo-Keto Reductases - metabolism; Bioactive compounds; Biomedical and Life Sciences; Biosynthesis; Biotechnological Products and Process Engineering; Biotechnology; Biotransformation; Cascade chemical reactions; Catalysis; Dehydrogenase; Dehydrogenases; Glutamate dehydrogenase; Glutamate Dehydrogenase - metabolism; Industrial applications; Industrial production; Life Sciences; Microbial Genetics and Genomics; Microbiology; Optical activity; Oxidation-Reduction; Phenylethyl Alcohol; Reductases; Stereoisomerism; Stereoselectivity; Transaminase; Transaminases; Transaminases - metabolism; Cascade reaction; α-Methylbenzylamine; ω-Transaminase; α-Phenylethanol
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-022-12299-x

  Chiral α-methylbenzylamine and α-phenylethanol are important building blocks for the industrial production of optically active drugs, bioactive compounds. Methods for the simultaneous synthesis of chiral α-methylbenzylamine and α-phenylethanol remain rare. Herein, a biocatalytic redox cascade reaction composed of ω-transaminase, aldo–keto reductase, and glutamate dehydrogenase for chiral α-methylbenzylamine and α-phenylethanol synthesis from racemic α-methylbenzylamine was constructed. A novel ω-transaminase and two different chiral aldo–keto reductases were demonstrated in the cascade reaction. The cosubstrate and redox equivalents were regenerated simultaneously by glutamate dehydrogenase. Using the approach, ( R )-α-phenylethanol, ( S )-α-phenylethanol, and ( R )-α-methylbenzylamine were prepared with excellent stereoselectivity ( ee  > 99.7%). Furthermore, semi-preparative-scale biotransformation of racemic α-methylbenzylamine was conducted. The production of ( R )-α-phenylethanol reached 26.05 mM at 24 h, and the production of ( S )-α-phenylethanol reached 25.44 mM at 32 h. Taken together, a novel idea was proposed for the efficient and green synthesis of chiral α-methylbenzylamine and α-phenylethanol, which had great potential for industrial application. Key points • Excellent stereoselectivity chiral α-methylbenzylamine and α-phenylethanol were synthesized. • A novel ω-transaminase demonstrated the catalysis toward (S)-α-methylbenzylamine. • Two novel aldo–keto reductases demonstrated the conversion toward acetophenone. Graphical Abstract