LARGE-SCALE PRODUCTION OF BUGULA NERITINA IN A CONTROLLED CULTURE SYSTEM TO PRODUCE CHEMICALLY CONSISTENT BRYOSTATIN 1

A CONTROLLED-ENVIRONMENT, AQUACULTURE SYSTEM IS PROPOSED FORHIGH-YIELD PRODUCTION OF THE MARINE BRYOZOAN, BUGULA NERITINL., AND ITS CHEMICAL CONSTITUENT, BRYOSTATIN (A SERIES OF 19MACROLACTONES). BRYOSTATIN 1 IS ENTERING CLINICAL TRIALS AS AN ANTINEOPLASTIC AGENT, AND PRESENTLY NO COMMERCIAL CHEMICAL SYNTHESIS OR MICROBIAL SOURCE EXISTS. SUPPLIES HAVE COME FROM EXTRACTIONS OF LARGE AMOUNTS OF OCEAN-COLLECTED BUGULA (YIELD = 0.2-0.6 PPM W.W.). THE PHASE I PROGRAM WILL CULTURE B. NERITINA (FROM CALIFORNIA PARENT STOCK) IN AQUARIA. BRYOSTATIN YIELDS WILLBE TESTED IN CULTURES FED EITHER ARTIFICIAL PLANKTON OR A MIXTURE OF NATURAL PLANKTON. THE FOODS THEMSELVES WILL ALSO BE ASSAYED FOR BRYOSTATIN CONTENT. A FEED THAT GIVES RELIABLE BRYOSTATIN PRODUCTION AT REASONABLE YIELDS IS NEEDED BEFORE A COMMERCIAL SYSTEM CAN BE OPERATED ECONOMICALLY. GOOD GROWTH AND YIELDS OF BUGULA ARE EXPECTED, AND IT IS ANTICIPATED THAT BRYOSTATIN WILL BE PRESENT IN AT LEAST ONE OF THE EXPERIMENTAL GROUPS. IN PHASE II AND SUBSEQUENT RESEARCH, SYSTEMS WILL BE DESIGNED TO DELIVER BRYOSTATIN 1 IN YIELDS ESTIMATED TO RANGE FROM 100 TO 120 GRAMS PER YEAR PER ACRE OF CULTURE SYSTEM. PRODUCTION COSTS WOULD BE COMPETITIVE WITH OCEAN COLLECTING, BUT PRODUCTION WOULD BE MORE RELIABLE.