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

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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.