The oceans have supplied substances which are pharmacologically active and useful in medicine and research. One of the most interesting compounds is the polyether okadaic acid which is produced by marine dinoflagellate algae (Dinophysis and Prorocentrum spp.). Okadaic acid is involved in causing two seafood-borne, chemically-induced human diseases, diarrhetic shellfish poisoning and ciguatera. In contrast, however, this monocarboxylic acid is a powerful molecular probe with tremendous commercial potential. At low concentrations (I x 10-7 M), okadaic acid caused a prolonged tonic contraction in human umbilical arteries and in guinea pig isolated ventricle muscles. These effects could be induced even during severe Ca2+ deficiency and this type of agent has not been previously reported. Subsequent studies have established okadiac acid as a specific inhibitor of protein phosphatase I and protein phosphatase 2A, two of the four major protein phosphatase enzymes in the cytosol of mammalian cells that dephosphorylate scrine and threonine residues. Okadaic acid is also a potent non-phorbol ester-type tumor promoter on mouse skin. Thus, okadaic acid is well established in the field of biomedical research. The aims of Phase I will be to determine the feasibility of obtaining commercial quantities of okadaic acid from cultures of Prorocentrum hoffmannianum. We will combine studies of innovative culturing techniques and physiological manipulation in order to optimize and economize okadaic acid production in this species.Awardee's statement of the potential commercial applications of the research:Commercialization is based upon large sales volumes of other polyether antibiotics and molecular probes. In addition, we have established retail markets with large chemical companies, as well as several individual biomedical researchers.National Cancer Institute (NCI)
