Alternative enzymatic pathways to penicillin antibiotics

Nature Communications, Published online: 30 April 2026; doi:10.1038/s41467-026-72466-w Penicillin derivatives remain among the most widely prescribed antibiotics. In this study, the authors report an alternative pathway to penicillins that uses standalone ligase and epimerase enzymes to generate peptide precursors, which can be transformed into penicillin derivatives using an engineered isopenicillin N synthase enzyme, providing direct access to therapeutically relevant penicillin G, penicillin