A close collaboration between teams from the universities of Leiden and Groningen succeeded in the total synthesis of the very complex molecule lugdunomycin and clarified its biosynthetic pathway, which included an intermolecular Diels-Alder reaction. They published their results in JACS.

Most drugs that enter clinical use are produced by microbes, 80% of which are based on natural products. Examples include penicillin, vancomycin and rapamycin. ‘Although we can’t seem to discover new antibiotics, there is still a lot of unexplored chemical space’, says Professor of Molecular Biotechnology, Gilles van Wezel. ‘Our labs are focused on discovering what new medicines are hiding in that space.’

Over ten years ago, PhD student Changsheng Wu discovered a new, highly complex compound in the Streptomyces strain QL37, called lugdunomycin (named after the Latin name for Leiden, Lugdunum). ‘Despite its complexity, Wu drew the structure almost completely correctly on the whiteboard’, Van Wezel recalls. ‘But even with a thousand agar plates, we could only produce a few hundred micrograms — nowhere near enough for a comprehensive analysis.’