腈水解酶的催化混乱性研究进展

Advances in the catalytic promiscuity of nitrilases

摘要:

腈水解酶作为一种重要的生物催化剂广泛应用于重要医药中间体的合成，它能高效地将腈基转化为酸和氨，其反应具有温和、绿色环保等优点。腈水解酶不仅具有催化腈生成对应羧酸产物的水解活性，即表现出催化专一性，还兼具催化腈生成酰胺的水合活力，即表现出催化混乱性。腈水解酶的催化混乱性具有两面性：酰胺副产物的存在增加了后续羧酸产物分离纯化的难度和成本；但若能精准调控腈水解酶的催化反应路径实现酶功能的重塑，可以拓宽腈水解酶生物催化的反应类型，为高值酰胺类化合物的生物合成提供新思路和工艺，这对人工酶的创制及生物催化均具有重要意义。本文结合近年来相关的研究成果，综述了当前腈水解酶催化混乱性的研究进展，并从腈水解酶的进化起源、催化结构域以及催化机理等方面，探讨可能影响腈水解酶催化混乱性关键调控因子，为腈水解酶在生物催化领域上的应用提供了借鉴和参考。

Abstract:

As important biocatalysts, nitrilases can efficiently convert nitrile groups into acids and ammonia in a mild and eco-friendly manner, being widely used in the synthesis of important pharmaceutical intermediates. Early studies reported that nitrilases only had the hydrolysis activity of catalyzing the formation of corresponding carboxylic acid products from nitriles, showing catalytic specificity. However, recent studies have shown that some nitrilases exhibit the hydration activity for catalyzing the formation of amides from nitriles, showing catalytic promiscuity. The catalytic promiscuity of nitrilases has dual effects. On the one hand, the presence of amide by-products increases the difficulties and costs of subsequent separation and purification of carboxylic acid products. On the other hand, however, if the catalytic reaction pathways of nitrilases can be precisely regulated to reshape enzyme functions, the reactions catalyzed by nitrilases can be broadened to provide new ideas for the biosynthesis of high-value amides, which is crucial for the development of artificial enzymes and biocatalysis. This review summarized the research progress in the catalytic promiscuity of nitrilases and discussed the key regulatory factors that may affect the catalytic promiscuity of nitrilases from the evolutionary origin, catalytic domains, and catalytic mechanisms, hoping to provide reference and inspiration for the application of nitrilases in biocatalysis.