微生物来源的γ内酰胺酶研究进展

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。

Advances in lactamases from microbes-A Review

gamma-Lactamase belongs to the amidase. The (+) gamma-lactamses can be applied in the kinetic resolution of racemic gamma-lactam, which can produce (-) gamma-lactam efficiently. The (-) gamma-lactam enantiomer is an important synthon for the synthesis of carbocyclic nucleosides. Up to now seven strains of microbes were reported that produced gamma-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 alpha/beta hydrolase family. However, no structure data and mechanism theory is available for (+) lactamase till now. The future works focus on protein engineering of the gamma-lactamase to improve the catalysis of the protein, elucidation of the catalytic mechanism of the gamma-lactamase and the functions of the gamma-lactamase in vivo.