BIOSYNTHETIC OPTIMIZATION OF BRYOSTATINS IN AQUACULTURE

该项目的商业目标是为 提高前景看好的抗癌药物Bryostatin 1的产量， 来自海洋苔藓动物Bugula neritina的养殖。Bryostatin 1， 目前正在进行治疗几种癌症的第二阶段临床试验， 不能经济地合成，必须从动物身上获得。 目前，该系统的Bryostatin 1产量不太理想(7-8亩 G/g vs.15-16微克/gdw)，部分是由于次优 实验室确定的猪日粮中生化前体的含量 殖民地。专有水产养殖饲料将得到补充 Bryostatin-1合成的特定必需脂类和已知前体 为了确定哪些组合能产生最大的生物质产量 还有毒品。Bryostatin 1的产量预计将增加两倍或更多。 确定哪种Bryostatin是bryostatin 1的前体将有所帮助 在设计最佳饮食方面。人的新陈代谢关系 将使用放射性标记的苔藓素来研究各种苔藓素类药物 在整个动物和无细胞实验中。改进后的技术将 允许CalBioOcean的水产养殖系统在经济上与 布格鲁种群的自然收集物 保持年复一年的大规模收成。 建议的商业应用： 提供显著增加的抗癌药物的总收率 复方苔藓抑素在L生物质生产中的应用 应用知识改善饮食的网纹布格拉水产品 生物合成机制，以及将前体物质添加到 饮食配方。Bryostatin产量-在2-3范围内的改进 目前的收益率被认为是可以达到的，因此大大减少了 生产成本，并使系统具有竞争力。

The commercial goal of this project is to develop technology for increasing the yield of the promising anticancer drug, bryostatin 1, from aquaculture of the marine bryozoan, Bugula neritina. Bryostatin 1, which is in Phase II clinical trials for treatment of several cancers, cannot be synthesized economically and must be obtained from the animal. Presently bryostatin 1 yields from the system are sub-optimal (7-8 mu g/g vs. 15-16 mu g/g dw from nature) due, in part, to sub-optimal amounts of biochemical precursors in the diet of laboratory-settled colonies. Proprietary aquaculture diets will be supplemented with specific essential lipids and known precursors of bryostatin 1 synthesis to determine which combinations induce the greatest yields of biomass and drug. Bryostatin 1 yields are expected to increase two-fold or more. Determining which bryostatin is the precursor to bryostatin 1 will help in designing the optimal diet. The metabolic relationships of the various bryostatins will be investigated using radiolabeled bryostatins in whole animal and cell-free experiments. The improved technology will allow CalBioMarine's aquaculture system to compete economically with natural collections of Bugulu neritina populations which could not sustain large-scale harvests on a year-to-year basis. PROPOSED COMMERCIAL APPLICATION: Provide for significant increases in overall yield of the anticancer compound bryostatin l in the biomass output from a commercial sea-based BuguLa neritina AquaPharm by improving diet through applying knowledge of the biosynthetic mechanisms, and addition of precursor substances to the diet formulation. Bryostatin yield-improvements in the range 2-3 times present yields are thought to be attainable, thus greatly reducing production costs, and allowing the system to be competitive.