Protein & Peptide Letters ( IF 1.0 ) Pub Date : 2021-10-31 , DOI: 10.2174/0929866528666210816114032 Deshuai Lou 1 , Xi Liu 1 , Jun Tan 1
7α-Hydroxysteroid dehydrogenase and 7β-hydroxysteroid dehydrogenase are key enzymes involved in bile acid metabolism. They catalyze the epimerization of a hydroxyl group through 7-keto bile acid intermediates. Basic research of the two enzymes has focused on exploring new enzymes and the structure-function relationship. The application research focused on the in vitro biosynthesis of bile acid drugs and the exploration and improvement of their catalytic ability based on molecular engineering. This article summarized the primary and advanced structural characteristics, specificities, biochemical properties, and applications of the two enzymes. The emphasis is also given to obtaining novel 7α-hydroxysteroid dehydrogenase and 7β-hydroxysteroid dehydrogenase that are thermally stable and active in the presence of organic solvents, high substrate concentration, and extreme pH values. To achieve these goals, enzyme redesigning based on protein engineering and genomics may be the most useful approaches.
中文翻译:
7α-和7β-羟基类固醇脱氢酶概述:结构、特异性和实际应用
7α-羟基类固醇脱氢酶和7β-羟基类固醇脱氢酶是参与胆汁酸代谢的关键酶。它们通过 7-酮胆汁酸中间体催化羟基的差向异构化。这两种酶的基础研究主要集中在探索新的酶及其结构-功能关系。应用研究集中在胆汁酸类药物的体外生物合成及其基于分子工程的催化能力的探索和提高。本文总结了这两种酶的初级和高级结构特征、特异性、生化特性和应用。重点还在于获得在有机溶剂存在下具有热稳定性和活性的新型 7α-羟基类固醇脱氢酶和 7β-羟基类固醇脱氢酶,高底物浓度和极端 pH 值。为了实现这些目标,基于蛋白质工程和基因组学的酶重新设计可能是最有用的方法。