甲酸脱氢酶及其在手性生物制造中的应用

Formate dehydrogenase and its application in biomanufacturing of chiral chemicals

摘要:

氧化还原生物合成体系在绿色生物制造手性化合物中具有重要应用价值。甲酸脱氢酶（formate dehydrogenase，FDH）能氧化甲酸盐生成二氧化碳，同时将NAD （P）⁺还原为NAD （P） H，是氧化还原生物合成中辅酶再生体系的关键酶。但天然的FDH催化效率低、稳定性差、辅酶利用率不高等缺点制约了其在工业生产中的应用。文中着重介绍了FDH的结构特征、催化机制以及不同来源FDH在酶活、催化效率、稳定性及辅酶偏好性改造方面的研究进展，同时总结了利用FDH作为辅酶再生系统进行绿色生物制造手性化合物的应用实例。

关键词:甲酸脱氢酶;分子改造;氧化还原生物合成;绿色生物制造

Abstract:

The redox biosynthesis system has important applications in green biomanufacturing of chiral compounds. Formate dehydrogenase (FDH) catalyzes the oxidation of formate into carbon dioxide, which is associated with the reduction of NAD(P)⁺ into NAD(P)H. Due to this property, FDH is used as a crucial enzyme in the redox biosynthesis system for cofactor regeneration. Nevertheless, the application of natural FDH in industrial production is hampered by low catalytic efficiency, poor stability, and inefficient coenzyme utilization. This review summarized the structural characteristics and catalytic mechanism of FDH, as well as the advances in protein engineering of FDHs toward improved enzyme activity, catalytic efficiency, stability and coenzyme preference. The applications of using FDH as a coenzyme regeneration system for green biomanufacturing of chiral compounds were summarized.

Key words:formate dehydrogenase;molecular modification;redox biosynthesis;green biomanufacturing