Discovery and antibacterial activity of kibdelomycin A-1 and A-2 from repeat batch fermentation of Kibdelosporangium banguiesne.

Kibdelomycin and kibdelomycin A are antibiotics biosynthesized by Kibdelosporangium banguiense CA-240109. Kibdelomycin demonstrates broad-spectrum activity, exhibiting significant activity against antibiotic-resistant Gram-positive bacteria. These compounds inhibit DNA GyrB and ParE through a distinct U-shaped multi-contact binding mechanism and do not display cross-resistance with established antibiotics. To investigate structure-activity relationships, various methodologies were employed to identify new congeners, including the implementation of repeat batch fermentation. This study presents the discovery, isolation, structural elucidation, and antibacterial assessment of two mono des-chloro congeners of kibdelomycin A produced via repeat batch fermentation. The newly discovered compounds displayed inhibitory effects on bacterial growth in Staphylococcus aureus and Escherichia coli, with minimum inhibitory concentrations (MIC) ranging from 16 to 64 μg/mL. The MIC values for E. coli are comparable to kibdelomycin, whereas for S. aureus the MIC is 64 times less potent than that of kibdelomycin. AI-assisted docking studies involving DNA gyrase B enzymes provide reasonable support for varying activities of the congeners.