Marine Bacillus Yields Two New Depsipeptides With Potent Activity Against Gram-Positive Bacteria

Chemists screening the culture broth of a marine-derived bacterium, Bacillus sp. ROA-056, have uncovered two previously unknown linear peptides, named pobacilamides A and B. The compounds were described in a study published in The Journal of Antibiotics on 23 October 2026, where researchers report that both molecules show selective antibacterial activity against Gram-positive bacteria.

The team worked out the planar structures of the two compounds using mass spectrometry together with one-dimensional and two-dimensional NMR analyses. Both peptides are built from the amino acid valine, 2-hydroxyisovaleric acid (HIVA) and 2-hydroxyisocaproic acid (HICA), while pobacilamide A additionally contains leucine.

To establish the absolute configurations of the valine and leucine residues, the researchers used acid hydrolysis followed by advanced Marfey’s method, a standard chromatographic approach for distinguishing amino acid enantiomers. The configurations of the two hydroxy acids, HIVA and HICA, were determined by gas chromatography–mass spectrometry after the acids were derivatized as O-trifluoroacetylated (S)-(+)-3-methyl-2-butyl esters. Together these analyses defined the complete stereochemical makeup of both new molecules.

Biological testing revealed a clear pattern of selectivity. Pobacilamides A and B inhibited Gram-positive bacteria, including Bacillus subtilis and Kocuria rhizophila, with minimum inhibitory concentrations ranging from 0.25 to 4 micrograms per milliliter. Pobacilamide B was the most potent of the pair, reaching an MIC of 0.25 micrograms per milliliter against K. rhizophila. In contrast, no antibacterial activity was observed against the Gram-negative strains tested.

The authors conclude that these results suggest the two compounds have considerable potential as targeted antibacterial agents for Gram-positive pathogens. As with any newly isolated natural product, the finding rests on laboratory assays reported in the abstract of the study; the compounds remain at an early stage of investigation, and the published summary does not include data on activity beyond the tested strains, mechanisms of action, or effects in any animal or clinical setting. The full data supporting the study are stated to be available within the article and its Supplementary Information.

Subject of Research: Discovery of two new linear depsipeptides from a marine-derived Bacillus sp. and their selective antibacterial activity against Gram-positive bacteria.

Article Title: Pobacilamides A and B, two linear depsipeptides from a marine-derived Bacillus sp. ROA-056

Article References: Lee, E.-Y., Kim, D.-A., Lee, J. Y., Lee, J., Choi, B., Paik, M.-J., Kim, H., Lee, S., Lim, K.-M., & Nam, S.-J. (2026). Pobacilamides A and B, two linear depsipeptides from a marine-derived Bacillus sp. ROA-056. The Journal of Antibiotics. https://doi.org/10.1038/s41429-026-00967-3

Image Credits: AI Generated

DOI: 10.1038/s41429-026-00967-3

Keywords: pobacilamides, depsipeptides, Bacillus, marine-derived bacteria, antibacterial activity, Gram-positive bacteria, MIC, NMR, Marfey's method, GC-MS, natural products, The Journal of Antibiotics