Newly discovered enzymes essential for bacterial defense can also help chemists characterize the stereochemistry of natural products. The enzyme cuts the protein between the abnormal amino acids. Breaks down large, difficult-to-handle lipopeptides into smaller pieces It’s easier to study that way (J.Am. Chemistry. society 2026, DOI: 10.1021/jacs.5c17955).

Researchers typically study natural products as molecules secreted by a single organism, but researchers in Pierre Stallforth’s lab wondered what happens when microorganisms cooperate. In 2020, he and a team at the Leibniz Institute for Natural Products Research and Infection Biology identified a pair of bacterial species. Pseudomonas genus seeds and Paenibacillus sp. Seed–that Work together to survive the amoeba attack (Procedure National Acad. Science. united states of america 2021, DOI: 10.1073/pnas.2013759118). When the species are separated, the bacteria become prey for the amoeba, but when they are together, they kill the would-be predator.

In previous research, Stallforth and colleagues traced the cooperative activity to natural products. Pseudomonas genus It produces species such as a leggy lipopeptide called syringafactin. of Paenibacillus sp. The seeds chop some syringafactin into small molecules that are deadly to the amoeba.

To analyze Paenibacillus sp. While enzymes were in play, Stallforth’s team learned from mutualistic microbes and collaborated on their own. He teamed up with Jud Helmich and Markus Reikmeier from the Friedrich Schiller University of Jena. In a new study, researchers found that Paenibacillus sp. They studied syringafactin and observed which enzyme-encoding genes the microbes express more. This led to the discovery of two unusual enzymes that are behind bacterial defense. DL-Peptidases, which break the bonds between. D– and L-amino acid.

Most amino acids in nature are L-Since the configuration LL– a peptidase that breaks the bond between two L-Amino acids are common. In comparison, DL-Peptidases are much rarer.

Importantly, the peptidase the researchers discovered did not cleave all DL bonds in syringafactin. Each recognizes its own DL join and leaves other joins untouched. “We were excited that the peptidase we found was actually very specific,” Helmich says. “That’s what gives them value.”

Roger Linton of Simon Fraser University, who was not involved in the study, agrees. Existing techniques for analyzing peptides containing DInstead, amino acids are often hydrolyzed as a whole into individual amino acids, he explains. If a peptide contains the same amino acid in both the D and L configurations, this analysis does not indicate where each is present. newly discovered DL-Peptidases can be ‘convenient’ by cleaving natural product molecules at specific positions, storing them as larger fragments, and revealing the D and L configurations of the amino acids on either side of the cut.

To demonstrate the utility of this enzyme, the three teams modified the peptidase to expand the types of DL peptide bonds it can cleave. The researchers also used the enzyme to characterize two natural products, tensin and WLIP, a large lipopeptide that is also produced. Pseudomonas genus Bacteria.

Beyond characterization, this discovery could help discover the biological activity of more natural products, especially if the molecules are modified through microbial collaboration. Recognizing that products naturally produced by some organisms may not be active ingredients is important for the natural products community to consider, Linton says.

The research team is looking for further examples of microbial cooperation involved in the modification of natural products and potentially creating more new enzymes. “We want to show that this is a ubiquitous phenomenon in nature,” Stallforth says. Meanwhile, researchers also DL– a peptidase to characterize new natural products – and they hope other research groups will also use this peptidase. “It’s certainly something we have in mind,” Linton said.