Abstract
Protein tags play an important role in various chemical biological applications and synthetic biological systems. An ideal protein tag enables labelling of proteins, their monitoring, and detection. Moreover, it forms a stable bond with its specific ligand, which is ideally an available and cheap molecule. Current protein tagging systems are often challenging due to unspecific binding, unstable coupling, or expensive and difficult-to-synthesize ligand molecules. Here, we present PenTag, an approach for the biorthogonal, and covalent conjugation of a specific protein tag to its ligand for various applications in chemical and synthetic biology. We engineered a new truncated version of penicillin-binding protein 3 (PBP3) and showed that this protein tag can be used for the stable conjugation of proteins to dyes, polymers, or solid supports. We applied PenTag as crosslinking tool for synthesizing stimuli-responsive hydrogels or for the development of a biohybrid material performing computational operations emulating a 4:2 encoder. Based on this broad applicability and the use of a small, cheap and easy-to-functionalize ligand and a stable, soluble recombinant protein, we see PenTag as a versatile alternative to existing protein tags.
Competing Interest Statement
The authors have declared no competing interest.
