Structure-function relationships of epoxide hydrolases and their potential use in biocatalysis
Structure-function relationships of epoxide hydrolases and their potential use in biocatalysis
复制标题
DOI：
10.1016/j.bbagen.2009.11.014
复制
发表时间：
2010-03-01
影响因子：
3
通讯作者：
Lindberg, Diana
中科院分区：
文献类型：
--
作者：
Widersten, Mikael;Gurell, Ann;Lindberg, Diana
背景：手性环氧化合物和二醇类化合物是精细化工和医药领域的重要合成物。环氧化物水解酶（EC 33.2）。-)催化环氧化物的水解开环，产生相应的相邻表盘。几种同工酶表现出催化特性，使它们成为产生对映纯环氧化合物和表盘的有前途的生物催化工具。综述范围：本文主要介绍了酶的结构和功能在生物催化方面的应用。讨论了用于立体定向开环、产生手性邻二醇和动力学分解机制以获得对映纯环氧化物的现有生物催化数据，并与酶催化剂的结构-活性研究结果相关联。最近的例子，酶的功能定向进化的概念也提出。主要结论：目前对环氧化物水解酶在化学催化方面的构效关系有较强的认识。随着研究的进行，对影响底物特异性和立体特异性的因素的更详细的看法有望出现。目前环氧化物水解酶在合成中的应用有望随着新酶的分离和表征而扩大。定向进化所需的催化和物理化学性质的改进方法可能进一步促进新的和有用的生物催化剂的发展。一般意义：酶的催化能力为开发用于生产有用化学品的高效、特定和可持续的技术提供了新的可能性。(C) 2009 Elsevier B.V.版权所有
Background: Chiral epoxides and diols are important synthons for manufacturing fine chemicals and pharmaceuticals. The epoxide hydrolases (EC 33.2.-) catalyze the hydrolytic ring opening of epoxides producing the corresponding vicinal dial. Several isoenzymes display catalytic properties that position them as promising biocatalytic tools for the generation of enantiopure epoxides and dials.Scope of review: This review focuses on the present data on enzyme structure and function in connection to biocatalytic applications. Available data on biocatalysis employed for purposes of stereospecific ring opening, to produce chiral vicinal diols, and kinetic resolution regimes, to achieve enantiopure epoxides, are discussed and related to results gained from structure-activity studies on the enzyme catalysts. More recent examples of the concept of directed evolution of enzyme function are also presented.Major conclusions: The present understanding of structure-activity relationships in epoxide hydrolases regarding chemical catalysis is strong. With the ongoing research, a more detailed view of the factors that influence substrate specificities and stereospecificities is expected to arise. The already present use of epoxide hydrolases in synthetic applications is expected to expand as new enzymes are being isolated and characterized. Refined methodologies for directed evolution of desired catalytic and physicochemical properties may further boost the development of novel and useful biocatalysts.General significance: The catalytic power of enzymes provides new possibilities for efficient, specific and sustainable technologies to be developed for production of useful chemicals. (C) 2009 Elsevier B.V. All rights reserved.