Heterologous Expression of Marine Natural Products

说明（申请人提供）：海洋天然产物化学结构多样，具有很强的生物活性，尤其是抗癌活性。 然而，由于其有限的供应，将这些化合物开发成临床药物受到阻碍。 Acera Biosciences，Inc.开发了一种在发酵中生产这些化合物的策略。 拟议的研究项目的重点是开发生产这些化合物的异源表达系统。 将使用新克隆的异戊酰胺生物合成途径作为测试途径，开发一组四种载体-宿主系统。 这些系统中的外源途径表达将在转录、翻译和功能水平上进行评估，以提供改进指导。 在下一阶段的实验中，将扩展和应用所得到的令人满意的系统来生产有价值的海洋天然产品。 该方法将缓解药物开发中一些有效的海洋天然产物的供应短缺。 此外，这将有助于扩大目前的抗癌药物试验，以更多的海洋天然产品，否则无法获得，因为供应有限。

DESCRIPTION (provided by applicant): Marine natural products are diverse in chemical structure and have great biological activities, especially anticancer activities. However, developing these compounds into clinical drugs has been hindered by their limited supply. Acera Biosciences, Inc. has developed a strategy to produce these compounds in fermentation. The proposed research project focuses on developing heterologous expression systems for the production of these compounds. Using the newly cloned barbamide biosynthetic pathway as a test pathway, a group of four vector-host systems will be developed. Foreign pathway expression in these systems will be evaluated at the transcription, translation, and functional levels to provide guidance for improvement. The resulting satisfactory system(s) will be extended and applied to produce valuable marine natural products in the next phase of experiments. The proposed method will alleviate the supply shortage of some potent marine natural products in drug development. Moreover, it will help to expand the current anticancer drug tests to more marine natural product that are otherwise unavailable because of limited supply.