腈水解酶在医药中间体生物催化研究中的最新进展  

Recent Progress in the Application of Nitrilase in the Biocatalytic Synthesis of Pharmaceutical Intermediates

作　　者：龚劲松 李恒 陆震鸣 史劲松 许正宏 

机构地区：[1]江南大学药学院,无锡214122

出　　处：《化学进展》2015年第4期448-458,共11页Progress in Chemistry

基　　金：国家自然科学基金项目(No.21406088;21206055);江苏省自然科学基金项目(No.BK20140133);'十二五'国家科技支撑计划课题(No.2012AA022204C)资助~~

摘　　要：腈水解酶是生物催化领域中的一种重要催化剂,可用于羧酸的生物合成,反应过程具有条件温和、催化效率高、选择性突出、工艺绿色环保等特点,在医药中间体的制备中具有重要应用,符合原子经济性和绿色化学的发展方向。相关酶种的挖掘及改造已逐步成为新的研究热点,许多腈水解酶催化剂已被开发应用于医药中间体的合成。随着现代分子生物学技术的进步以及生物催化进入第三次发展浪潮,利用基因工程手段构建的基因工程菌或纯化酶作为催化剂已变得较为普遍,提高催化剂的催化潜力、改善其催化特性以最大程度的体现腈水解酶合成反应的独特优势,将为腈水解酶应用于更多医药中间体的合成奠定基础。本文综述了用于医药中间体合成的腈水解酶的应用与发展现状,并探讨了该领域研究所面临的前所未有的机遇与挑战。Nitrilase is a crucial enzyme in the field of biocatalysis, which can be used for biosynthesis of various carboxylic acids from corresponding nitriles. This approach is usually employed for preparing pharmaceutical intermediates because of its superior catalytic characteristics including mild reaction conditions, high conversion efficiency, prominent selectivity, and eco-friendly nature. Therefore, the nitrilase-mediated biocatalysis conforms to the development directions of atom economy and green chemistry. It has drawn substantial attention from scholars and entrepreneurs due to its application potential. Several studies have been performed to explore its application in synthesis of several pharmaceutical intermediates and numerous nitrilases have been developed as the industrial catalysts. Whereas, mining and modification of nitrilases are gradually becoming research focuses. Moreover, with the rapid advances of modern molecular biology as well as the advent of the third wave of biocatalysis, gene engineering has become a common approach for constructing recombinant strains. The significant advantages of nitrilase-mediated biocatalysis can be represented in maximum degree through improving the catalytic activity of nitrilase and modifying its catalytic properties, which would lay the foundation for more applications of nitrilases in the future. In this review, the application and development for the synthesis of pharmaceutical intermediates with nitrilase are summarized, as well as unprecedented opportunities and challenges in this field are discussed.

关 键 词：腈水解酶 医药中间体 生物催化 有机酸 

分 类 号：Q55[生物学—生物化学] Q819