Structure-based mechanisms: On the way to apply alcohol dehydrogenases/reductases to organic-aqueous systems

Alcohol dehydrogenases/reductases catalyze enantioselective syntheses of versatile chiral compounds relying on direct hydride transfer fromcofactor 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/reductaseswhich 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. (c) 2020 Published by Elsevier B.V.

Automated summary

This study summarizes the structures and behaviors of alcohol dehydrogenases/reductases in organic-aqueous systems, comparing the structures of enzymes with different tolerance towards organic solvents. By understanding the catalytic mechanisms of these enzymes in organic-aqueous systems, the efficient enantioselective syntheses mediated by alcohol dehydrogenases/reductases and further challenges are discussed through solvent engineering and enzyme immobilization in the last decade.