COPROPHILOUS FUNGI--NEW SOURCES OF BIOACTIVE METABOLITES

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Many useful drugs have been discovered through studies of microbial natural products. However, coprophilous (dung-colonizing) fungi have not been widely studied for secondary metabolite production. Antagonism between species of coprophilous fungi has been the subject of numerous literature reports. Compounds responsible for such effects are essentially natural antifungal agents, which may also exhibit other use useful bioactivities. We propose that coprophilous fungi comprise a potentially valuable source of new natural products with pharmacological activity. Therefore, we intend to undertake studies of the secondary metabolites of selected coprophilous fungi in search of novel compounds with antifungal, antibiotic, antiviral, antitumor, and other potentially useful bioactivities. Our approach to this research in non-random, since it is based on the application of literature evidence and ecological rational. Coprophilous fungal species chosen for our study will be those which have been reported in the literature to exhibit antagonistic effects toward competitors, those which occur late in coprophilous fungal successions, and those which are closely related to coprophilous fungi that have already yielded antifungal agents in our preliminary studies. Fresh isolates of coprophilous fungal species will be obtained through a subcontractual, collaborative agreement with Prof. D. Malloch of the Univ. of Toronto, and expert in the field of coprophilous mycology. Standardized prescreens of culture filtrates, chromatographic fractions, and purified metabolites for antifungal and antibiotic activities will be conducted in our laboratory, and a battery of 25 screens for other bioactivities (antiviral, antifungal, antitumor, immunomodulatory, etc.) will be conducted by a cooperating pharmaceutical company (Schering Corporation). In-house antifungal screens will include tests against natural competitors and medically relevant fungi. Assays of metabolites against metabolites. Initial results indicate that a high percentage of the coprophilous fungal isolates that we have chosen to screen do exhibit antifungal activity, and several antifungal agents have been isolated through these preliminary investigations. These studies are closely aligned with our long-term interest in fungal metabolites of pharmacological and ecological significance. Relatively little is known of the chemical ecology of microbial ecosystems, despite the importance of microbial metabolites in modern medicine. Through our studies in this area, we expect to explore the natural products chemistry of a seldom-studies fungal class, while evaluating the potential of an ecologically-based approach to the discovery of novel bioactive agents.