Pestalone, a new antibiotic produced by a marine fungus in response to bacterial challenge

The isolation and structure determination of a new chlorinated benzophenone antibiotic, pestalone (1), is described. The new compound was produced by a cultured marine fungus only when a unicellular marine bacterium, strain C NJ-328, was co-cultured in the fungal fermentation. The fungus, isolated fr om the surface of the brown alga Rosenvingea sp. collected in the Bahamas I slands, was identified as an undescribed member of the genus Pestalotia. Th e structure of 1, initially assigned with only modest confidence by combine d spectral and chemical data, was confirmed by single-crystal X-ray analysi s. Pestalone (1) exhibits moderate in vitro cytotoxicity in the National Ca ncer Institute's 60 human tumor cell line screen (mean GI(50) = 6.0 muM). M ore importantly, pestalone shows potent antibiotic activity against methici llin-resistant Staphylococcus aureus (MIC = 37 ng/mL) and vancomycin-resist ant Enterococcus faecium (MIC = 78 ng/mL), indicating that pestalone should be evaluated in advanced models of infectious disease.