An international team of scientists has created a molecular movie of an enzyme building a key structure found in penicillin antibiotics, capturing fleeting chemical reactions that have never been seen before in such detail.
Using powerful X-rays, researchers from the University of Oxford in collaboration with partners from the XFEL Hub at Diamond Light Source, Lawrence Berkeley National Laboratory, PAL-XFEL and SLAC National Accelerator Laboratory, captured the enzyme in action, revealing the unexpected process of how nature builds its antibiotic structure.
By taking a series of ultrafast X-ray snapshots, the researchers were able to piece together a molecular movie showing the previously unseen rapid chemical stages in the formation of β-lactam antibiotics like penicillin.
The study, published in Nature Catalysis, focuses on isopenicillin N synthase (IPNS), an enzyme responsible for a crucial step in the biosynthesis of penicillin antibiotics.
The work is the result of more than a decade of international collaboration and reveals unexpected aspects of the chemistry that could help inform the development of new antibiotics and other therapeutics.
Image: Structure of the human enzyme AspH. The enlarged view shows the enzyme’s iron-containing active site (orange sphere) bound to its protein substrate. Using time resolved X-ray crystallography, the researchers observed how AspH activates oxygen and hydroxylates proteins, providing new insight into a family of enzymes involved in oxygen sensing, development and cancer.
Credit: Patrick Rabe/University of Oxford and Greg Stewart/SLAC National Accelerator Laboratory