USE OF CHEMICAL ECOLOGY TO PRODUCE ECTEINASCIDINS

受控集约化水产养殖中的环境控制 系统将被用来提高天然产品的生产 由海洋被囊藻Eteinascidia turbinata产生的胞外杀菌素。第一阶段 研究将考察6个环境因素对内毒素的影响 生产：光照强度、温度、喂食率、无机氮 浓度、无机磷浓度与模拟捕食 组织损伤。复制菌落将在流动中保持不变 海水水族箱在不同处理方案下8周。治疗 被发现显著影响ecteinassidin产生的将被结合在 持续8周的另一系列实验，以确定协同效应 效果。这些关于化学生态的调查结果 将被囊类应用于水产养殖生产 第二阶段研究中的外源性杀菌素。 外膜蛋白，仅以微量形式存在于被膜中 (.0000001-.00000001)，目前正处于临床前开发阶段 抗癌剂。开发可靠的候选药物来源 是满足预期的研究、临床和市场需求所必需的。 该项目的成功完成将使水产养殖增加 这种高价值药物的产量，可能会减少产量 成本增加了一个或多个数量级。高产水产养殖 生产方法，基于对化学生态的知识 生产生物，也可应用于其他海洋无脊椎动物的药物 目前，制药流水线。

Environmental manipulations within controlled, intensive aquaculture systems will be used to enhance the production of the natural product ecteinascidins by the marine tunicate Ecteinascidia turbinata. The Phase I study will examine the effects of 6 environmental factors on ecteinascidin production: light intensity, temperature, feeding rate, inorganic nitrogen concentration, inorganic phosphate concentration and simulated predation tissue damage. Replicate colonies will be maintained in flow-through seawater aquaria for 8 weeks under different treatment regimes. Treatments found to significantly affect ecteinascidin production will be combined in a further series of experiments lasting 8 weeks to identify synergistic effects. The results of these investigations of the chemical ecology of the tunicate will be applied to the aquacultural production of the ecteinascidins in the Phase II study. The ecteinascidins, which are present in only trace amounts in the tunicate (.0000001 -.00000001), are presently in preclinical development as anticancer agents. Development of a reliable source of the drug candidate is necessary to meet the projected research, clinical and market demands. 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. High-yield aquaculture production methods, based on a knowledge of the chemical ecology of the producing organisms, can also be applied to other marine invertebrate drugs presently the pharmaceutical pipeline.