BIOSYNTHETIC OPTIMIZATION OF BRYOSTATINS IN AQUACULTURE

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Biochemical and biosynthesis information will be used to formulate an optimal diet for the aquacultural production of the natural product drug bryostatin 1 by the marine bryozoan Bugula neritina. Phase I will: 1) develop methods for whole animal biosynthesis experiments; 2) determine which sterols and fatty acids are produced de novo by the bryozoan and which must be obtained from the diet; and 3) establish the basic biosynthetic pathway for bryostatin production. Phase II will further define the bryostatin biosynthesis; identified limiting biosynthetic and lipid building blocks will then be incorporated into enriched artificial diets and evaluated for their potential to increase bryostatin 1 yield in aquaculture systems already under development by CalBioMarine. Bryostatin 1 is presently in clinical development as an antileukemic agent. Development of a reliable source of the drug is necessary to meet the projected clinical and market demand. 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. Biosynthetic methods for optimization of aquaculture feeds for high-yield production of natural products, once developed, can also be applied to other marine invertebrate drugs presently in the pharmaceutical pipeline.