The discovery of enfumafungin, a novel antifungal compound produced by an endophytic Hormonema species 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 vitro against Candida and Aspergillus and with moderate efficacy in an in vivo mouse model of disseminated candidiasis. The agent is especially interesting since its antifungal spectrum and its effect on morphology of Aspergillus fumigatus is comparable to that of the glucan synthase inhibitor pneumocandin B,,, the natural precursor of the clinical candidate MK-0991 (caspofungin acetate). An additional search for other Hormonema isolates 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 Hormonema strains 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 Kabatina species. Kabatina is a coelomycetous genus whose members are known to produce Hormonema-like states in culture.

Hyalodendrosides A and B, antifungal triterpenoid glycosides from a lignicolous hyphomycete, Hyalodendron species.

Two antifungal triterpenoid glycosides, hyalodendrosides A and B (1 and 2), were isolated from a solid matrix fermentation of a lignicolous hyphomycete, Hyalodendron sp. Their structures were determined based upon extensive examination of spectral parameters, particularly NMR and MS data. Both compounds have beta-linked glucose moieties. Compounds 1 and 2 show weak to moderate antifungal activity against some clinically relevant fungi.

A novel inositol mono-phosphatase inhibitor from Memnoniella echinata. Producing organism, fermentation, isolation, physicochemical and in vitro biological properties.

A novel inositol mono-phosphatase inhibitor, L-671,776 (1), was discovered from a culture of the hyphomycete, Memnoniella echinata (ATCC 20928). 1 has a molecular weight of 388 and a molecular formula of C23H32O5. The mode of inhibition is non-competitive, with a Ki of 450 microM. It shows no inhibition of myo-inositol 1,4-bisphosphate 1-phosphatase or myo-inositol 1,4,5-triphosphate 5-phosphatase, although it weakly inhibits myo-inositol 1,4,5-triphosphate 3-kinase (IC50 = 3 mM). It elevates inositol monophosphates in rat parotid slices (EC50 approximately 3 mM), but abolishes agonist effects. It also produces short-lived contraction of guinea pig trachea at 300 microM.