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

这个小型企业技术转让(STTR)第一阶段项目旨在开发一种可持续生产棕榈醇和棕榈皂苷的方法，这是一种来自海洋的有效抗炎萜类化合物。总的来说，该提案所涉及的问题是缺乏一种具有商业意义的海洋衍生萜烯的生产方法。该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，以有效地生产这一海洋天然产品家族。这个第一阶段的提案由两个独立但相关的目标组成：(1)完成生物合成途径的研究，以确定涉及岩藻糖苷生物合成的生物合成转化；(2)评估新岩藻糖苷和相关代谢物的抗炎活性，以确定该家族中最具生物活性的化合物(S)。事实证明，海洋环境是一种极其丰富的新型天然产物来源，具有各种生物检测活动。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的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变为商业实体的重大障碍。从软珊瑚Eunicea fusca中分离出来的褐藻糖苷和褐藻糖苷是一类海洋天然产品的一个例子，其开发因缺乏可用供应而受到阻碍。

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.