Biochemical and biosynthetic optimization of bryostatin 1 in Bugula neritina

Bryostatin 1 is a macrocyclic lactone isolated from the marine bryozoan Bugula neritina. It is currently in clinical trials at the National Cancer Institute as a promising new antileukemic agent. Bryostatin 1 is found in Bugula neritina in poor yields (10^-4% dry weight). The focus of this research was to develop the biochemical and biosynthetic techniques that could be utilized to optimize the production of bryostatin 1 in Bugula neritina through aquaculture. To that end, the basic biosynthetic pathway to bryostatin 1 in the marine bryozoan was evaluated by using radiolabeled precursors. Techniques for the incorporation of these precursors were also developed. Other experiments involved an analysis of the composition of a specific population of Bugula neritina in terms of its bryostatin and lipid content. A determination of which lipids are produced de novo and which are exogenous was also undertaken.