Discovery of new bioactive secondary metabolites from bacteria in extreme habitats

As part of our efforts to explore structurally and biologically novel secondary metabolites from unique environments for drug discovery, we have investigated secondary metabolites of actinomycete strains inhabiting in the Arctic Ocean, tidal mudflats, and Alaskan permafrost. First, arcticoside and C-1027 chromophore-V, were isolated from a culture of an Arctic marine Streptomyces strain. These new compounds, bearing a benzoxazine ring, inhibited Candida albicans isocitrate lyase. Second, buanmycin and buanquinone, were discovered from the culture of a marine Streptomyces strain, from a tidal mudflat. The structure of buanmycin was determined by X-ray crystallographic analysis and NMR experiments including ¹³C-¹³C COSY. Lastly, we isolated bacterial strains from Alaskan permafrost samples. Buanmycin strongly inhibited the pathogenic Gram-negative bacterium Salmonella enterica (MIC = 0.7µM). In particular, buanmycin demonstrated inhibition of sortase A, which is a promising target for antibiotic discovery.