微生物来源的γ内酰胺酶研究进展

Advances in lactamases from microbes-A Review

摘要:

摘要：γ-内酰胺酶属于酰胺酶，其中的（+）γ-内酰胺酶能够高效率的动力学拆分外消旋体γ-内酰胺，获得光学纯的（-）γ-内酰胺。光学纯的（-）γ-内酰胺是制备抗病毒药物碳环核苷化合物的重要手性中间体。目前报道共有7个来源于微生物的γ-内酰胺酶，其中来源于Aureoacterium sp.的（-）γ-内酰胺酶的晶体结构获得了解析。根据晶体结构推测的（-）γ-内酰胺酶的催化机理与α/β水解酶超家族的催化机理是类似的。但是，目前还没有（+）γ-内酰胺酶的晶体结构模型的数据及机理的描述。γ-内酰胺酶的研究方向主要包括γ-内酰胺酶的蛋白质工程改造，对不同对映体选择性的γ-内酰胺酶的催化机理的阐述，以及γ-内酰胺酶在生物体内的功能研究。

Abstract:

Abstract: γ-Lactamase belongs to the amidase. The (+) γ-lactamses can be applied in the kinetic resolution of racemic γ-lactam, which can produce (-) γ-lactam efficiently. The (-) γ-lactam enantiomer is an important synthon for the synthesis of Carbocyclic Nucleosides. Up to now 7 strains of microbes were reported that produced γ-lactamses. The crystal structure of (-) lactamase from Aureoacterium sp. was resoluted, and the catalytic mechanism based on the structure data analysis was alike with the α/β hydrolase family. However, no structure data and mechanism theory is available for (+) lactamase till now. The future works focus on protein engineering of the γ-lactamase to improve the catalysis of the protein, elucidation of the catalytic mechanism of the γ-lactamase and the functions of the γ-lactamase in vivo.