Microbial Tag-Team: Researchers Decode Joint Defense Strategy of Bacteria
A team at the Cluster of Excellence "Balance of the Microverse" reveals how two bacterial species cooperate to modify a chemical weapon against predators—a discovery with potential applications in drug development.
In the microscopic world, cooperation is a matter of survival. Researchers in Jena have deciphered the molecular rules of a fascinating alliance between two soil bacteria, Pseudomonas and Paenibacillus. While one bacterium produces a chemical compound, the other sharpens it into a deadly weapon to fend off predatory amoebae. The study, published today in the Journal of the American Chemical Society (JACS), offers new insights into microbial ecology and provides a new tool for analyzing complex natural products.
Turning a Shield into a Sword
In 2021, a team led by Prof. Pierre Stallforth at the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI) first observed that these two bacteria join forces. Now, in collaboration with Prof. Ute Hellmich and Dr. Markus Lakemeyer, they have uncovered the exact mechanism.
The process relies on syringafactin, a lipopeptide produced by Pseudomonas. On its own, this molecule is relatively harmless. However, Paenibacillus produces specific enzymes—known as DL-peptidases—that act like molecular scissors. They cut the syringafactin at a specific, unusual site. This modification transforms the molecule into a potent toxin that kills the predatory amoeba.
Mirror Images and Molecular Scissors
The study highlights a chemical rarity. "Amino acids in nature are usually 'left-handed' (L-configured)," explains Prof. Pierre Stallforth. "Most enzymes are designed to cut these standard forms." However, the enzymes discovered here target 'right-handed' (D-configured) structures—molecular mirror images that look identical in composition but differ in spatial arrangement. "This is like trying to put a right-handed glove on a left hand; it requires a very specific fit," adds Prof. Ute Hellmich.
From Ecology to Biotechnology
Beyond understanding microbial warfare, this discovery has practical applications. The newly identified enzymes can be used as tools to analyze other complex natural substances. "We can use them to selectively cut large molecules into smaller, readable fragments," says Dr. Markus Lakemeyer. This could significantly speed up the discovery of new antibiotics and other medicines derived from nature.
The "Jena Spirit" of Collaboration
The success of the study is attributed to the close interdisciplinary network in Jena. "Individually, none of us would have been able to tackle this problem," notes Hellmich. The project spanned from chemical analysis and structural biology to ecological studies, involving the Leibniz-HKI, University of Jena, and the University of Würzburg.
The work was supported by the Cluster of Excellence "Balance of the Microverse," the Collaborative Research Centre ChemBioSys, and the Werner Siemens Foundation.
Original Publication
Zhang S, Huang Y, Schlabach K, Tran M A, Nachawati R, Bader N, Komor A J, Hertweck C, Schindelin H, Lakemeyer M*, Hellmich U A*, Stallforth P* (2026). Microbial DL-Peptidases Enable Predator Defense and Facilitate Structure Elucidation of Complex Natural Products. JACS. DOI: 10.1021/jacs.5c17955