Abstract
Aldo-keto reductases (AKRs) mediated stereoselective reduction of prochiral carbonyl compounds is an efficient way of preparing single enantiomers of chiral alcohols due to their high chemo-, enantio-, and regio-selectivity. To date, the application of AKRs in the asymmetric synthesis of chiral alcohols has been limited, due to the challenges of cloning and purifying. In this work, the aldo-keto reductase (AKR3-2-9) from Bacillus sp. was obtained, purified and proved to be NADPH-dependent. It exhibits good bioactivity and stability at 37 °C, pH 6.0. AKR3-2-9 is catalytically active on 11 pairs of substrates such as 3-methylcyclohexanone and methyl pyruvate, among which it showed the highest catalytic activity for acetylacetone. In addition, AKR3-2-9 was able to be resistant to five common organic solvents such as methanol and ethanol, it retained high catalytic activity even in a reaction system containing 10% v/v organic solvent for 6 h, which indicates its broad substrate spectrum and exceptional organic solvent tolerance. Furthermore, its three-dimensional structure was constructed and catalytic-site-analysis of the enzyme was conducted. Notably, it was capable of catalyzing the reaction of the key intermediates of duloxetine. The extensive substrate spectrum and predominant organic solvents resistance makes AK3-2-9 a promising enzyme which can be potentially applied in medicine synthesis.
Highlights
Chiral alcohols are compounds with hydroxyl groups on the chiral carbon atoms
Chiral alcohols can be synthesized by chemical methods which were proved to be harsh for the complicated preparation process, severe environmental pollution and low selectivity of the product enantiomer [7,8]
The results showed that AKR3-2-9 has a broad substrate spectrum and excellent organic solvent tolerance, making it a promising biocatalyst for the synthesis of chiral alcohols
Summary
Chiral alcohols are compounds with hydroxyl groups on the chiral carbon atoms Based on this structure, other sites may have different functional groups or substituents, such as aromatic alcohols, fatty alcohols, and transoxides [1,2,3]. Other sites may have different functional groups or substituents, such as aromatic alcohols, fatty alcohols, and transoxides [1,2,3] Chiral alcohols and their derivatives are important intermediates of the synthesis of chiral drugs [4], chiral pesticides and many chemical materials like liquid crystal materials, they play an increasingly important role in medicine and other chemical fields [5,6]. Biocatalytic synthesis of chiral alcohols provides an efficient strategy in the preparation of pharmaceutical intermediates [11], which is a green and sustainable synthetic route [12]
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