BIOSYNTHETIC OPTIMIZATION OF BRYOSTATINS IN AQUACULTURE

生化和生物合成信息将用于制定一种 天然产物药物水产养殖生产的最佳饲料 Bryostatin 1由海洋苔藓虫Bugula neritina.第一阶段：1) 建立全动物生物合成实验方法；2)测定 哪些甾醇和脂肪酸是由苔藓虫从头产生的，以及 必须从饮食中获得；以及3)建立基本的 苔藓生长抑素的生物合成途径。第二阶段将进一步 定义苔藓抑制素生物合成；确定限制生物合成 然后将脂质构建块结合到浓缩的 人工饲料及其增加潜力的评估 Bryostatin 1在已经开发的水产养殖系统中的产量 加州生物海军。 Bryostatin 1目前作为一种抗白血病药物处于临床开发阶段。 探员。开发可靠的药物来源是必要的，以满足 预计的临床和市场需求。成功完成这项工作 项目将使水产养殖产量增加这一高价值 制药，可能会降低一个或多个订单的生产成本 规模之大。优化水产养殖的生物合成方法 用于高产生产天然产品的饲料一旦开发出来，就可以 也适用于其他海洋无脊椎动物药物 制药管道。

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.