Abstract
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.
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All data generated or analyzed during this study are included in this published article.
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This work was supported by the funding for school-level research projects of Yancheng Institute of Technology (xjr2022035).
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X.H.Y. elaborated the study. J.B.L. and M.Y.W collected the data. J.B.L. and C.L contributed to the data analysis and drafted the article. H.X.D. and X.H.Y. contributed to the critical revision of the manuscript. J.B.L. contributed to the funding acquisition. All authors read and approved the final manuscript.
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Liu, J., Wang, M., Liang, C. et al. Redox cascade reaction for kinetic resolution of racemic α-methylbenzylamine and biosynthesis of α-phenylethanol. Appl Microbiol Biotechnol 107, 125–135 (2023). https://doi.org/10.1007/s00253-022-12299-x
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DOI: https://doi.org/10.1007/s00253-022-12299-x