The Discovery of Enfumafungin, a Novel Antifungal Compound Produced by an Endophytic HormonemaSpecies Biological Activity and Taxonomy of the Producing Organisms

In a screening of natural products with antifungal activity derived from endophytic fungi, we detected a potent activity in a culture belonging to the form-genus Hormonema, isolated from leaves of Juniperus communis. The compound is a new triterpene glycoside, showing an antifungal activity highly potent in vitroagainst Candidaand Aspergillusand with moderate efficacy in an in vivomouse model of disseminated candidiasis. The agent is especially interesting since its antifungal spectrum and its effect on morphology of Aspergillus fumigatusis comparable to that of the glucan synthase inhibitor pneumocandin Bo, the natural precursor of the clinical candidate MK-0991 (caspofungin acetate). An additional search for other Hormonemaisolates producing improved titers or derivatives resulted in the isolation of two more strains recovered from the same plant host showing identical activity. The producing isolates were compared with other non-producing Hormonemastrains by DNA fingerprinting and sequencing of the rDNA internal transcribed spacers. Comparison of rDNA sequences with other fungal species suggests that the producing fungus could be an undetermined Kabatinaspecies. Kabatinais a coelomycetous genus whose members are known to produce Hormonema-like states in culture.