Isolation and structural elucidation of pelgipeptin E, a novel pore-forming pelgipeptin analog from Paenibacillus elgii with low hemolytic activity.

Pelgipeptins are cyclic lipopeptides composed of nine amino acids and a short fatty acid chain. In the present study, we report a novel pelgipeptin peptide that was isolated from Paenibacillus elgii BC34-6 and named pelgipeptin E (PGP-E). The molecular mass of PGP-E was 1072 Da as determined by liquid chromatography-mass spectrometry and the amino acid sequence was elucidated by tandem mass spectrometry. The complete molecular structure of PGP-E was characterized using 2D NMR spectroscopy. PGP-E consisted of a cyclic peptide backbone of Dab1-Val2-Dab3-Phe4-Leu5-Dab6-Val7-Leu8-Ser9 and a lipid chain (-CH2CH2CH3). PGP-E had broad antimicrobial activity against gram-negative and -positive bacteria, including methicillin-resistant Staphylococcus aureus strains. Furthermore, the mode of action of PGP-E was investigated using calcein dye leakage and membrane depolarization assays, which suggest that PGP-E acts via a membrane-active mechanism. The hemolytic activity of PGP-E was significantly lower than that of melittin, a well-known membrane-active peptide derived from bee venom. These results suggest that PGP-E is a potential candidate in the development of new peptide antibiotics.