苏氨酸醛缩酶的催化机理、分子改造及合成应用

Catalytic mechanism, molecular engineering and applications of threonine aldolases

摘要:

苏氨酸醛缩酶催化醛和甘氨酸羟醛缩合，一步反应即可构建产物β-羟基-α-氨基酸的两个手性中心，从原子经济性和环境影响角度，是非常具有潜力的绿色合成光学纯β-羟基-α-氨基酸的方式之一。多个不同生物来源的苏氨酸醛缩酶得到分离和表征，较低的β-碳立体选择性以及反应过程中动力学和热力学控制难题，使其在合成应用中面临很大挑战。文中综述了近年来苏氨酸醛缩酶在基因挖掘、催化机理、高通量筛选与分子改造、合成应用等方面的研究进展，旨在为进一步研究提供参考。

Abstract:

Threonine aldolases catalyze the aldol condensation of aldehydes with glycine to furnish β-hydroxy-α-amino acid with two stereogenic centers in a single reaction. This is one of the most promising green methods for the synthesis of optically pure β-hydroxy-α-amino acid with high atomic economy and less negative environmental impact. Several threonine aldolases from different origins have been identified and characterized. The insufficient b-carbon stereoselectivity and the challenges of balancing kinetic versus thermodynamic control to achieve the optimal optical purity and yield hampered the application of threonine aldolases. This review summarizes the recent advances in discovery, catalytic mechanism, high-throughput screening, molecular engineering and applications of threonine aldolases, with the aim to provide some insights for further research in this field.