USE OF CHEMICAL ECOLOGY TO PRODUCE ECTEINASCIDINS

ENVIRONMENTAL MANIPULATIONS WITHIN CONTROLLED, INTENSIVE AQUACULTURE SYSTEMS WILL BE USED TO ENHANCE THE PRODUCTION OF THE NATURAL PRODUCT ECTEINASCIDINS BY THE MARINE TUNICATE ECTEINASCIDIA TURBINATA. THE PHASE I STUDY WILL EXAMINE THE EFFECTS OF 6 ENVIRONMENTAL FACTORS ON ECTEINASCIDIN PRODUCTION: LIGHT INTENSITY, TEMPERATURE, FEEDING RATE, INORGANIC NITROGEN CONENTRATION, INORGANIC PHOSPHATE CONCENTRATION AND SIMULATED PREDATION TISSUE DAMAGE. REPLICATE COLONIES WILL BE MAINTAINED IN FLOW-THROUGH SEAWATER AQUARIA FOR 8 WEEKS UNDER DIFFERENT TREATMENT REGIMES. TREATMENTS FOUND TO SIGNIFICANTLY AFFECT ECTEINASCIDIN PRODUCTION WILL BE COMBINED IN A FURTHER SERIES OF EXPERIMENTS LASTING 8 WEEKS TO IDENTIFY SYNERGISTIC EFFECTS. THE RESULTS OF THESE INVESTIGATIONS OF THE CHEMICAL ECOLOGY OF THE TUNICATE WILL BE APPLIED TO THE AQUACULTURAL PRODUCTION OF THE ECTEINASCIDINS IN THE PHASE II STUDY. THE ECTEINASCIDINS, WHICH ARE PESENT IN ONLY TRACE AMOUNTS IN THE TUNICATE (.000001 -.0000001), ARE PRESENTLY IN PRECLINICAL DEVELOPMENT AS ANTICANCER AGENTS. DEVELOPMENT OF A RELIABLE SOURCE OF THE DRUG CANDIDATE IS NECESSARY TO MEET THE PROJECTED RESEARCH, CLINICAL AND MARKET DEMANDS. SUCCESSFUL COMPLETION OF THIS PROJECT WILL ENABLE INCREASED AQUACULTURE YIELDS OF THIS HIGH-VALUE PHARMACEUTICAL, POSSIBLY REDUCING PRODUCTION COSTS BY ONE OR MORE ORDERS OF MAGNITUDE. HIGH-YIELD AQUACULTURE PRODUCTION METHODS, BASED ON A KNOWLEDGE OF THE CHEMICAL ECOLOGY OF THE PRODUCING ORGANISMS, CAN ALSO BE APPLIED TO OTHER MARINE INVERTEBRATE DRUGS PRESENTLY THE PHARMACEUTICAL PIPELINE.