Quadoctomycin, a 48-membered macrolide antibiotic from Streptomyces sp. MM168-141F8

Drug-resistant bacteria are still emerging, and screening of new skeletal antibiotics is important. During our continuous screening for antimicrobial agents, we discovered a new antimicrobial, named quadoctomycin, from solid culture of Streptomyces sp. MM168-141F8. The substance was purified by solvent extraction, silica gel chromatography and HPLC. Structural elucidation of quadoctomycin was performed by MS and NMR analyses and chemical degradation. Quadoctomycin possesses a 48-membered polyol macrolide skeleton in which an α-D-mannoside is connected to C-22 by an O-glycosidic linkage. The structure of quadoctomycin was found to be related to that of monazomycin A based on the analyses of NMR spectra in the same solvent (pyridine-d5). Quadoctomycin showed potent antibacterial activity against Staphylococcus aureus, including methicillin-resistant S. aureus, and other Gram-positive pathogenic bacteria such as Enterococcus faecalis and E. faecium (including drug-resistant strains), but did not show activity toward Gram-negative bacteria or Candida albicans.