The overall commercial aim of this project is to discover and develop novel therapeutic drug leads against diverse therapeutic targets from symbiotic marine dinoflagellate algae using multidisciplinary approaches. Using newly developed cell-based screening technologies, novel biochemical structures of antiviral and anticancer drug leads will be identified in extracts of cultured symbiotic strains of dinoflagellates isolated from diverse marine invertebrates. Culture protocols will employ various media and stress conditions to induce metabolite production. Based on knowledge of the known bioactive metabolites from free-living dinoflagellates, many or most of the bioactive leads from symbiotic strains are expected to be polyketides. Degenerate PKS primers will be used to amplify PKS gene sequences. Specific marine dinoflagellate polyketide synthase (PKS) probes will be designed and utilized to identify PKs sequences in both cultured (Phase I) and uncultured (Phase II) symbiotic dinoflagellates separated from invertebrate hosts. The PKS sequences will be cloned, sequenced, and ultimately expressed (Phase II) in a new recombinant system. This innovative research should not only yield novel drug leads, but it should also validate our methods for developing PKS libraries from the large number of uncultured (including uncultuurble) marine dinoflagellates and other microorganisms in the oceans. PROPOSED COMMERCIAL APPLICATIONS: Discovery and heterologous expression of polyketide synthase genes from symbiotic marine dinoflagellates for commercial-scale fermentation of new polyketide-based therapeutic agents for the treatment and cure of cancer and viral diseases.
