Ultrafast X-Ray Snapshots Reveal Fleeting Steps in Penicillin Biosynthesis
Published in Biology, Drugs development & discovery, Journals, Tools.
Publication date: October 9, 2026.
University of Oxford researchers and international collaborators have captured short-lived chemical intermediates in the enzyme reaction that builds penicillin’s core structure. The findings were announced on October 9 alongside publication in Nature Catalysis.
The team studied isopenicillin N synthase (IPNS), which transforms a linear peptide into penicillin’s ring system. Ultrafast X-ray free-electron laser measurements provided successive structural snapshots, revealing a thioaldehyde intermediate and a monocyclic beta-lactam intermediate before the complete scaffold formed.
To initiate and time the reaction, researchers placed droplets containing oxygen-free enzyme microcrystals on moving tape and exposed them to oxygen. Adjusting the tape’s speed controlled the interval before each X-ray measurement. Combining the snapshots reconstructed stages of the reaction rather than relying on a single static enzyme structure.
The work also implicated internal water molecules and enzyme movements in guiding the chemistry. These mechanistic insights could support enzyme engineering and the design of alternative antibiotic scaffolds. The study does not demonstrate a new antibiotic treatment, improved patient outcomes, or a solution to antimicrobial resistance.
Sources: University of Oxford, October 9, 2026; Nature Catalysis study.