| Ecological considerations have not traditionally been applied in the search for new biologically active metabolites from microbial sources, but evidence suggests that such considerations could be utilized. The fungal sclerotium represents a critical survival structure in the life cycle of many fungal species, including members of the widespread genus Aspergillus. It is likely that sclerotia are frequently exposed to fungivorous insects, because they typically remain dormant in soil for extended periods of time. Therefore, natural selection may have guided the evolution and intrafungal allocation of metabolically costly chemical defenses.; Sclerotia were produced by solid substrate fermentation, powdered, and extracted. Bioassays using the insects Helicoverpa zea and Carpophilus hemipterus were used to guide the isolation of metabolites. Extracts were fractionated using different chromatographic techniques to yield pure compounds. Structure elucidation of these compounds was accomplished using high-field NMR experiments, as well as other spectroscopic techniques.; Extracts from the sclerotia of A. sulphureus yielded a variety of new indole-derived metabolites, including radarins A-D, sulpinines A-C, and analogs of penitrem B, many of which exhibit significant activity against H. zea and/or C. hemipterus. Studies of the distribution of these metabolites within the various fungal tissues indicate that these compounds are almost exclusively restricted to the sclerotia. Three new bicoumarins, isokotanins A-C, and several other known compounds were isolated from the sclerotia of A. alliaceus.; A freshwater fungal isolate, Pseudeurotium indicum, was also examined because of its unique ecological niche. This species, grown in liquid culture, yielded euroticin, a new antifungal and antibacterial metabolite with an unusual 1-oxaspiro (4.5) decane ring system.; The results of these studies indicate that evolutionary considerations may well provide useful leads in the discovery of new natural products with biological activities. |
