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

Through the intensive investigation of the chemical components for the culture broth of marine-derived Bacillus sp. ROA-056, two new linear peptides, namely, pobacilamides A (1) and B (2), have been discovered. Their planar structures were elucidated through mass spectrometry, and 1D and 2D NMR analyses. Both peptides were composed of valine (Val), 2-hydroxyisovaleric acid (HIVA), and 2-hydroxyisocaproic acid (HICA), while pobacilamide A (1) contained leucine (Leu). The absolute configurations of Val and Leu were defined by acid hydrolysis and advanced Marfey's method, while those of HIVA and HICA were established by GC-MS analysis of O-trifluoroacetylated (S)-(+)-3-methyl-2-butyl ester. Compounds 1 and 2 displayed selective antibacterial activity against Gram-positive bacteria, including Bacillus subtilis and Kocuria rhizophila, with minimum inhibitory concentrations (MICs) values from 0.25 μg/mL to 4 μg/mL. Pobacilamide B (2) showed the strongest activity against K. rhizophila with an MIC of 0.25 μg/mL. No antibacterial activity was observed against Gram-negative strains. These results suggested that compounds 1 and 2 have considerable potential as targeted antibacterial agents for Gram-positive pathogens.