Fungi are well known as prolific producers of biologically active natural products. A significant number of these metabolites have found importance as pharmaceuticals or agrochemicals, or as useful lead compounds in the development of such agents. The vast majority of known fungal metabolites have been isolated by mass random screening programs, primarily employing soil isolates. However, the fungi investigated to date represent only a small fraction (perhaps 5%) of estimated fungal biodiversity, as many fungi are niche-selective, and many ecological niches remain relatively unexplored as sources of fungi for screening.

Fungi are known to participate in many different types of antagonistic interactions in nature. Some types of fungi commonly display inhibitory effects toward competitor fungi. Mycoparasitic fungi attack and colonize host fungi. Many fungal species are associated with diseases of plants or insects, while others are resistant to attack by insects. In many cases, such effects are associated with the production of bioactive secondary metabolites by the "antagonist". Given the widespread recognition that studies of the chemical ecology of plants, insects, and marine organisms can serve as useful guides to the discovery of bioactive natural products, there is every reason to believe that investigation of ecological relationships among fungi could help to focus studies on species that produce bioactive agents.

The central hypothesis guiding our research program is that ecological and taxonomic information can enable rational selection of specific types of fungi as sources of bioactive natural products. Results from our studies of several targeted ecological groups of fungi have provided considerable evidence in support of this hypothesis. Moreover, because the niches being sampled are underinvestigated as sources of fungi for screening, many unusual or rarely explored taxa are encountered. For example, our studies of fungi that exert inhibitory effects on competitors (and fungi that attack and colonize others) have been very effective in leading to isolation of natural antifungal agents, and a significant percentage of these metabolites were previously unreported.

Our studies to date have led to the isolation of over 250 new fungal metabolites, nearly all of which show biological activity. Some of these compounds are similar to those previously known, while others are quite novel. Some intriguing chemical consistencies among taxonomic and ecological groups have also been encountered. Interestingly, a significant number of other compound-types accessed through this work were reported in the same time frame by industrial screening programs. Ultimately, it is clear that studies of a limited number of carefully chosen, well-characterized fungal cultures can provide access to a considerable range of chemical diversity. Such an approach is especially useful in a laboratory where resources do not permit mass screening, and can serve as a complement to ongoing industrial screening efforts. Details of some representative studies in this area will be provided in this presentation.