Isolation of cyclic decapeptide antibiotics related to gramicidin S

Natural products remain to be an important source for the development of antibacterial agents. In this study, we isolated and evaluated the key biological properties of minor components of the gramicidin S (GS) antibiotic complex produced by <i>Bacillus brevis</i> var. G-B R⁺. Using HPLC techniques, we obtained highly pure samples of GS and its five major related components in individual form. Structures of isolated compounds were assigned as GS homologues, featuring several amino acid residue substitutions, two of which are previously undescribed. Antibacterial activity of new cyclic decapeptides was close to GS, while two of five isolated compounds demonstrated up to 4 times reduced haemolysis. Circular dichroism spectra of GS homologues and the parental antibiotic exhibited the same β-structure conformation. Taken together, this study demonstrates that analysis of minor components of antibiotic complexes could result in the discovery of new antibacterial compounds with better efficacy or favourable therapeutic profile.