Oxford researchers capture real-time molecular movie of penicillin formation

Researchers from the University of Oxford and an international team of collaborators have captured a real-time molecular movie of the enzymatic process that forms the penicillin ring structure. Published in Nature Catalysis, the study uses X-ray free-electron lasers to observe the enzyme isopenicillin N synthase (IPNS) as it converts a linear peptide substrate into the characteristic β-lactam ring system.

By using powerful X-ray pulses to take structural snapshots at different reaction intervals, the team was able to observe fleeting intermediate stages that had remained unobserved for over four decades. The research reveals how the enzyme achieves this complex transformation in a single step, including the role of water in guiding the reaction.

While the study does not report a new antibiotic or clinical trial, the findings provide critical mechanistic insights into how nature constructs β-lactam antibiotics. This knowledge is considered a vital step toward replenishing the antibiotic pipeline and engineering new enzymes to combat rising antimicrobial resistance.