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At this year’s Leibniz Conference on Bioactive Compounds, held on April 28 and 29 in Aachen, the peptide pyrofactin has been selected as Leibniz Drug of the Year 2026. A research team from the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI) and the Friedrich Schiller University Jena has discovered this molecule and deciphered its key role in a previously unknown bacterial early warning and defense system.
New drugs do not arise solely in the test tube. They often originate from natural products that microorganisms produce in interaction with their environment. However, the functions these molecules fulfill in their natural context are still poorly understood. The award-winning research, conducted within the Cluster of Excellence “Balance of the Microverse”, demonstrates how rewarding this shift in perspective can be. Instead of focusing solely on the pharmaceutical potential of natural products, the team investigated their role within complex microbial communities.
Innovative approach reveals previously unknown natural product
The awarded study focuses on the interaction between the widespread bacterium Pseudomonas syringae and the predatory amoeba Polysphondylium pallidum. The researchers showed that the bacterium uses a chemical “radar” to detect and specifically eliminate these predators. This process relies on a sophisticated chemical signaling cascade: The bacterium produces the natural product syringafactin and releases it into its surroundings. When this molecule encounters the amoeba, it is chemically modified. The bacterium, in turn, possesses a dedicated sensor protein that recognizes these modified molecules as a warning signal and activates targeted defense mechanisms. As a result, the bacterium produces a second natural product: pyrofactin, a compound that is lethal to the amoebae.
The team led by Pierre Stallforth, professor at the University of Jena and deputy director of Leibniz-HKI, succeeded in elucidating this previously unknown mechanism and identifying pyrofactin as a promising new chemical structure. This discovery is more than an isolated finding. It exemplifies an innovative research approach that specifically investigates the dynamics of natural products — their transformation and function within interactions between different organisms — to uncover previously hidden compounds. Such substances could serve as the basis for new medicines or find applications in crop protection.
New opportunities for drug discovery
“The dynamics of natural products hold enormous, as yet largely untapped potential for the discovery of new bioactive compounds. This is precisely where new opportunities for drug discovery lie,” says Stallforth, who accepted the award in Aachen on behalf of his team.
The study also underscores the importance of interdisciplinary collaboration at the Leibniz-HKI. By combining expertise from different fields, even complex microbial interactions can be deciphered. The Cluster of Excellence “Balance of the Microverse” and the Collaborative Research Center ChemBioSys actively foster this interdisciplinary approach to natural product research in Jena.
Prof. Dr. Pierre Stallforth
Paleobiotechnology
Head of Department
pierre.stallforth@leibniz-hki.de
Zhang S, Schlabach K, Pérez Carrillo VH, Ibrahim A, Nayem S, Komor A, Mukherji R, Chowdhury S, Reimer L, Trottmann F, Vlot AC, Hertweck C, Hellmich UA, Stallforth P (2025) A chemical radar allows bacteria to detect and kill predators. Cell 188(9): 2495–2504.e20. https://doi.org/10.1016/j.cell.2025.02.033
The plant-pathogenic bacterium Pseudomonas syringae (center) uses a chemical radar to detect amoebae ...
Source: Luo Yu
Copyright: Leibniz-HKI
Award ceremony in Aachen: Pierre Stallforth (center) receives the certificate for the Leibniz Drug o ...
Source: Bernd Rupp
Copyright: Leibniz-FMP
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