Catcher/Tag Toolbox: Biomolecular Click-Reactions For Protein Engineering Beyond Genetics

Manipulating protein architectures beyond genetic control has attracted widespread attention. Catcher/Tag systems enable highly specific conjugation of proteins in vivo and in vitro via an isopeptide-bond. They provide efficient, robust, and irreversible strategies for protein conjugation and are simple yet powerful tools for a variety of applications in enzyme industry, vaccines, biomaterials, and cellular applications. Here we summarize recent development of the Catcher/Tag toolbox with a particular emphasis on the design of Catcher/Tag pairs targeted for specific applications. We cover the current limitations of the Catcher/Tag systems and discuss the pH sensitivity of the reactions. Finally, we conclude some of the future directions in the development of this versatile protein conjugation method and envision that improved control over inducing the ligation reaction will further broaden the range of applications. Catcher/Tag pairs enable protein conjugation via an isopeptide-bond mediated biological Click-reaction. In this review, we summarize the existing toolbox of Catcher/Tag pairs as well as the currently existing versatile applications of the Catcher/Tag pairs. Finally, we review the pH sensitivity of the reaction and discuss future outlooks towards further improved control and efficiency of the reactions.image