微生物谷胺酰胺转氨酶在蛋白质修饰中的应用

Recent Applications of Microbial Transglutaminase in Protein Modificaiton

谷胺酰胺转氨酶能催化蛋白质中谷氨酰胺与赖氨酸间的酰基转移反应,广泛应用于食品、纺织等工业。近年来,微生物来源的谷胺酰胺转氨酶,具有易得、反应条件温和、不依赖钙离子调节等优点,被广泛应用于蛋白质的定点修饰。通过基因工程手段,在蛋白质的特定部位引入谷胺酰胺转氨酶特异性识别的Q-Tag和K-Tag,谷胺酰胺转氨酶能催化抗体与小分子之间、蛋白质与蛋白质之间、蛋白质与聚合物之间、蛋白质与糖类物质之间、蛋白质与脂质体之间的定点偶联以及短肽的自身环化。这些蛋白质定点修饰产物在药物化学、化学生物学以及生物材料等领域有着广泛的用途。本文作者综述了近年来微生物谷胺酰胺转氨酶在蛋白质定点修饰中的最新进展。

Transglutaminases are a family of enzymes to ligate the carbonyl group of glutamines and the ε-amine group of lysine to form an amide bond between proteins. This conjugation technology was widely used in food and textile industry initially. Recently,microbial transglutaminases(MTGase) mediated ligation was developed into a useful tool for site-specific modification of protein because of the advantages,such as easy availability,mild reaction condition and Ca2+-independent etc. By introducing MTGase recognized Q-tag and K-tag into protein using genetic engineering technology,many molecules,including small molecular drugs,proteins,polymers,oligosaccharides and lipids are conjugated to proteins,and peptide cyclized through this site-specific acyl transfer reaction. These conjugates were extensively used in the fields of medicinal chemistry,chemical biology and biomaterials. This review focused on the recent progress of MTGase mediated site-specific protein modification.