Chemical investigations of endophytitc and fungicolous fungi

Fungal infections of crops and humans are widespread, and the costs associated with their prevention and treatment highlight a need for new antifungal agents. In addition, increased antimicrobial resistance enhances the need for new classes of antibiotics. Fortunately, fungi themselves are a rich source of bioactive secondary metabolites, including some clinically useful antifungal agents.

The role of fungi as decomposers sometimes results in these organisms being parasitic, mutualistic, or commensal with other organisms in their ecological communities. Such interspecies relationships are commonly associated with the production of biologically active compounds. The research described in this thesis involves studies of fungi from different ecological niches as part of an ongoing search for new bioactive natural products. Chapters 2-4 in this thesis describe investigations of secondary metabolites produced by selected fungal endophytes of corn. Endophytic fungi are those that grow in association with a plant host. Our group has previously reported the occurrence of antifungal pyrrocidines and phytotoxic dihydroresorcylide analogues from the maize-protective endophyte Acremonium zeae. The further studies discussed in this thesis describe bioactive secondary metabolites produced by isolates of three other endophytic fungal species. While no new natural products were discovered through these studies, antifungal and antiinsectan activities of the known metabolites encountered were determined for the first time. In addition, LCMS methods were developed for two of these endophytes in efforts to detect fungal metabolites in infected plant tissues as a key step towards exploring the protective and/or infectious roles these fungi and their metabolites may have in their plant hosts. The second group of studies presented focus on the secondary metabolites produced by three Hawaiian fungicolous fungal isolates. Previous studies of such fungi in our group have resulted in the identification of many new antifungal metabolites. The work presented here describes five new antifungal and/or antiinsectan natural products, as well as nine previously reported metabolites and a new compound generated during the isolation process. A variety of chromatographic techniques were used to isolate the compounds described in these studies, with the final step in most cases being HPLC. Structure elucidation of metabolites was accomplished primarily through analysis of 1D- and 2D-NMR and HRMS data.