Discovery of a Serine‐Directed Chemical Reaction for Site‐Specific Protein Modification via Phage Display Screening

-mediated hydroxyl-arylation reaction. CASA enables fast and precise modification of a single serine hydroxyl group within complex proteins while leaving the other amino acids, including serines at other sites, unmodified. CASA demonstrates robust performance in on-demand modification of diverse recombinant proteins, including therapeutic antibodies, with single-residue precision. The system's ability to selectively target individual proteins within crude cell lysates suggests its potential for applications in complex biological environments and positions it as a versatile tool for protein engineering.