| The marine environment is a prolific source of novel compounds for therapeutic use due to the complex biological and chemical diversity. Throughout the past 30-40 years, over 15,000 natural products have been discovered from the oceans, many of which display a broad range of potential clinical and commercial applications. Many marine invertebrates are sessile organisms that lack physical protection, and which chemical defense may be a possible explanation for these secondary metabolites. Despite the promise marine natural products have as potent pharmaceutical agents, one of the major factors delaying clinical use is the supply issue. These bioactive compounds are often found in trace amounts in the host organism, which makes harvesting from the reefs unfeasible. A general goal in our 10 was to investigate the biosynthesis of secondary metabolite terpenes to ultimately provide a production method of these potent marine derived compounds.;Eleutherobin and desmethyleleutherobin are diterpenes isolated from the Caribbean soft coral Erythropodium caribaeorum. These extremely valuable anticancer agents disrupt cell division by polymerizing and stabilizing microtubules, and have demonstrated tumor tissue selectivity toward selected breast, renal, ovarian and lung cancer cell lines. Determining the first intermediate in terpene biosynthesis is the initial step in developing a biotechnological production method of these cytotoxic agents. We investigated the complex chemistry of this coral using a radioactivity-guided isolation procedure, and isolated and partially characterized a diterpene hydrocarbon from E. caribaeorum .;The close association between marine invertebrates, zooxanthellae and numerous bacteria gives rise to the question of the identity of the producer of secondary metabolites in marine organisms. If the symbiont produces these therapeutic agents, cell culture methods could be employed to supply the compounds rather than obtaining them from coral reefs. Sesquiterpenes have been isolated from the gorgonian Plexaurella spp., however, no investigations concerning host/symbiont contribution of the sesquiterpenes have been reported. We investigated the biosynthetic source of terpenes in this coral, and experimental evidence indicates that bacteria are responsible for sesquiterpene production. We also examined sesquiterpene variation of Plexaurella spp. from various locations, and found sesquiterpene content to vary within and between species, identifying Plexaurella as a chemically indistinguishable genus. |
