Catalytic Site Analysis and Characterization of a Solvent-Tolerant Aldo-Keto Reductase

Chiral alcohols are important intermediates of various drugs. Compared with traditional chemical methods, the biocatalytic methods used for the synthesis of chiral alcohols exhibits many advantages, such as mild conditions and high enantioselectivity. Aldo-keto reductases are regarded as promising enzymes that can be potentially applied in the biocatalytic synthesis of chiral alcohols. In this study, a novel aldo-keto reductase, AKR7-2-1, was cloned and purified, and its important conserved sites were analyzed. In addition, this study analyzed the catalytic potential of AKR7-2-1. The optimum reaction conditions were studied; AKR7-2-1 showed excellent thermal stability and pH stability even when the temperature reached 80Ê°C or pH reached 9.0. Furthermore, AKR7-2-1 has strong enzymatic activity when 11 ketone-containing compounds are used as substrates, indicating the broad substrate spectrum of the enzyme. Most importantly, AKR7-2-1 has superior organic solvent tolerance even in an organic solvent of 30% volume per volume (V/V) or 10 hours in a 10% V/V organic solvent, where 60% enzyme activity was retained. It is worth mentioning that AKR7-2-1 can catalyze the reduction of N,N-dimethyl-3-keto-3-(2-thienyl)-1-propanamine to (S)-N,N-dimethyl-3-hydroxy-3-(2-thienyl)-1-propanamine, an intermediate of the antidepressant drug duloxetine. All this shows that AKR7-2-1 has broad application prospects in the field of biomedicine.

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About the authors

Wei Jiang*, wjiang@hqu.edu.cn, Rui Pei, Weiliang Wu, PanPan Zhao, Libing Tian, and Shu-Feng Zhou*, szhou@hqu.edu.cn, are all at the College of Chemical Engineering, Huaqiao University, Fujian, China. Wei Jiang and Rui Pei contributed equally to this work.

*To whom correspondence should be addressed.

Peer-Reviewed

Article submitted: Feb. 2, 2019
Article accepted: April 4, 2019

Article Details

BioPharm International
Volume 32, No. 7
July 2019
Pages: 34–40

Citation

When referring to this article, please cite it as W. Jiang et al., "Design Considerations for a Commercial Cell and Gene Therapy Facility," BioPharm International 32 (7) 2019.