STTR Phase I: Biosynthesis and Pharmacology of the Fuscosides: Potent Marine-Derived Anti-Inflammatory Agents

这个小企业技术转让（STTR）第一阶段项目旨在开发一种可持续生产fuscol和fuscosides的方法，fuscosides是一种海洋来源的强效抗炎萜烯。总的来说，提案中所处理的问题是缺乏一种具有商业意义的海洋衍生萜烯生产方法。本项目将采用的方法是将完整的生物合成基因簇或关键的生物合成基因克隆到可发酵的细菌中，以有效生产这一系列海洋天然产品。该I期提案由两个独立但相关的目标组成：（1）完成生物合成途径阐明研究，以鉴定涉及fuscol/fuscoside生物合成的生物合成转化，以及（2）评价新的fuscoside和相关代谢物的抗炎活性，以鉴定该家族中最具生物活性的化合物。海洋环境已被证明是具有各种生物测定活性的新型天然产物的极其丰富的来源。海洋覆盖了地球表面的70%以上，很明显，化学家和药理学家才刚刚开始触及海洋生物生物医学潜力的表面。然而，这些制剂的供应问题是将海洋天然产品转化为商业实体的一个重大障碍。从软珊瑚Eunicea fusca中分离出的Fuscol和fuscosides是一类海洋天然产品的一个例子，由于缺乏可用的供应，这些产品的开发受到了阻碍。

This Small Business Technology Transfer (STTR) Phase I project aims to develop a sustainable production method of fuscol and fuscosides, a family of potent anti-inflammatory terpenes of marine origin. In general, the issue being addressed in the proposal is the lack of a commercially relevant production method of marine-derived terpenes. The approach to be pursued in this project is to clone either the complete biosynthetic gene cluster, or key biosynthetic genes, into a fermentable bacterium for the efficient production of this family of marine natural products. This phase I proposal is comprised of two separate but related goals: (1) completion of biosynthetic pathway elucidation studies to identify the biosynthetic transformations involved in fuscol/fuscoside biosynthesis, and (2) evaluation of the anti-inflammatory activity of new fuscosides and related metabolites to identify the most bioactive compound(s) within this family. The marine environment has proven to be an extremely rich source of novel natural products with activities in a variety of biological assays. The oceans cover over 70% of the Earths surface, and it is clear that chemists and pharmacologists are only beginning to scratch the surface of the biomedical potential of marine organisms. However, the question of supply of these agents presents a significant hurdle in the transformation of the marine natural product into a commercial entity. Fuscol and fuscosides, isolatedfrom the soft coral, Eunicea fusca, represent one example of a class of marine natural products whose development has been hampered by the lack of an available supply.