Encrypting Chemical Reactivity in Protein Sequences toward Information‐Coded Reactions

Controlling chemical reactivity has been the central theme in chemistry. Herein, we review the recent progress on the development of genetically encoded protein coupling reactions and their potential applications. The chemical reactivity is encoded in the protein sequences. The information is read out by folding and molecular recognition between two reactive components and subsequently translated into chemical bonding via autocatalysis. It has emerged as a unique way to tune the chemical reactivity and is regarded as one type of information‐coded reactions. Not only has it received many applications such as protein topology engineering, bioconjugation, biomaterials and synthetic biology, but also its principle may be extended beyond protein chemistry to enable new modes of supramolecular interactions that promote chemical bonding and that are simultaneously reinforced by covalent bonds. We summarize the recent development of genetically encoded peptide‐protein coupling reactions and their diverse applications. It represents a novel way to tune chemical reactivity by the information encoded in the protein sequence, which is read out by protein folding and molecular recognition and translated into chemical bonding. The principles may be extended to enable new modes of supramolecular interactions that are coupled with covalent bonding.