Key Laboratory of Industrial Biotechnology of Ministry of Education & School of Biotechnology, Jiangnan University, Wuxi 214122, PR China; Department of Biological Science, Columbia University, New York, NY 10025, United States.
Key Laboratory of Industrial Biotechnology of Ministry of Education & School of Biotechnology, Jiangnan University, Wuxi 214122, PR China.
Int J Biol Macromol. 2021 Jan 31;168:412-427. doi: 10.1016/j.ijbiomac.2020.12.068. Epub 2020 Dec 11.
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.
醇脱氢酶/还原酶通过辅酶与底物之间或与中间体之间的直接氢转移，催化各种手性化合物的对映选择性合成。由于醇脱氢酶/还原酶催化的大多数底物不溶于水相，因此人们越来越关注有机-水相体系。然而，醇脱氢酶/还原酶通常在有机溶剂中不稳定，导致对映选择性合成效率不高。这些酶在有机溶剂中的原子水平行为尚不清楚，因此了解其在有机-水相体系中的结构基础机制对于提高其相对稳定性具有重要意义。在这里，我们总结了在有机-水相体系中结晶的醇脱氢酶/还原酶的可及结构，并比较了对有机溶剂具有不同耐受性的醇脱氢酶/还原酶的结构。通过了解这些酶在有机-水相体系中的催化行为和机制，讨论了通过醇脱氢酶/还原酶介导的高效对映选择性合成以及过去十年中通过溶剂工程和酶固定化所面临的进一步挑战。
