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.