Investigation of marine-derived fungi for bioactive natural products

The projects described in this dissertation are mainly focused on exploration of marine-derived fungi as a source of new pharmacologically active natural products. Fungi are prolific sources of medically useful secondary metabolites. Currently, fungi from marine habitats are relatively unexplored when compared to their terrestrial counterparts. The chemistry from marine-derived fungi is reviewed in Chapter 1.; Chapter 2 describes fermentation studies performed on a series of marine-derived fungi. Although the fungi are not obligate marine fungal species, they are highly salt tolerant and some show increased production of antimicrobial secondary metabolites when cultured in the presence of artificial seawater. Overall, Chapter 2 summarizes the antimicrobial activities of nine fungal isolates that were grown using six different concentrations of artificial seawater.; A class of antimicrobial farnesylated epoxycyclohexenones, the yanuthones, is described in Chapter 3. The yanuthones were isolated from an Aspergillus niger obtained from the tissue homogenate of an orange Aplidium sp. tunicate. The fermentation, the isolation, the structural elucidation, and the antimicrobial activities are discussed.; Chapter 4 describes the first chemical investigation of a Penicillium brocae. P. brocae is a rare species that had been formally described concurrently with the investigation described in Chapter 4. Fermentation of the P. brocae isolate resulted in the production of a novel class of polyketides, brocaenols A, B, and C. Additionally, the known metabolites, epicorazine A and B were isolated from P. brocae . The cytotoxic activity of epicorazine A is also briefly discussed.; Chapter 5 describes two novel metabolites from a new Penicillium sp. obtained from the alga Dictyosphaeria versluyii. The isolation, structural elucidation, and antibacterial activity of two novel polyketides, dictyosphaeric acid A and B, is presented.; Chapter 6 is the only chapter that does not involve marine-derived fungi. Rather, the antibacterial properties of the highly modified diterpenoid kalihinol class of sponge metabolites are presented. The chemistry of two Acanthella cavernosa sponges is reported and includes the description of two new kalihinol analogs, 10-formamido-kalihinol F and 15-formamido-kalihinol F. The studies presented in Chapter 6 show that some kalihinols inhibit bacterial folate biosynthesis.