Alcohol dehydrogenases/reductases catalyze enantioselective syntheses of versatile chiral compounds relying on direct hydride transfer from cofactor to substrates, or to an intermediate and then to substrates. Since most of the substrates catalyzed by alcohol dehydrogenases/reductases are insoluble in aqueous solutions, increasing interest has been turning to organic-aqueous systems. However, alcohol dehydrogenases/reductases are normally instable in organic solvents, leading to the unsatisfied enantioselective synthesis efficiency. The behaviors of these enzymes in organic solvents at an atomic level are unclear, thus it is of great importance to understand its structure-based mechanisms in organic-aqueous systems to improve their relative stability. Here, we summarized the accessible structures of alcohol dehydrogenases/reductases in Protein Data Bank crystallized in organic-aqueous systems, and compared the structures of alcohol dehydrogenases/reductases which have different tolerance towards organic solvents. By understanding the catalytic behaviors and mechanisms of these enzymes in organic-aqueous systems, the efficient enantioselective syntheses mediated by alcohol dehydrogenases/reductases and further challenges are also discussed through solvent engineering and enzyme-immobilization in the last decade.
Keywords: Alcohol dehydrogenases/reductases; Enzyme immobilization; Organic-aqueous system; Solvent engineering; Structure-based mechanism.
Copyright © 2020. Published by Elsevier B.V.