Cell Culture Production of Marine-Derived Bioactive Terpenses

DESCRIPTION (provided by applicant): The marine environment has proven to be a prolific source of novel bioactive molecules with great potential in a number of therapeutic areas. Currently, marine natural products are in clinical trials for cancer, analgesia, allergy and cognitive diseases. It is clear that research groups will continue to identify new marine natural products which offer great potential in many disease areas; however, it is equally clear that the question of the supply of these compounds presents a significant hurdle in their development as therapeutic agents. This project will focus on the development of a sustainable production method of terpenes from marine gorgonians. These organisms are the source of such terpenes as the pseudopterosins, potent anti-inflammatory agents, and eleutherobin, a potent microtubule stabilizing agent. Currently, these compounds are only available from large scale collections of the producing coral. We have recently found that the dinoflagellate symbiont of the gorgonian Pseudopterogorgia elisabethae is capable of pseudopterosin biosynthesis. Importantly, we have also determined that pseudopterosin production continues in cell culture of these microalgae. We aim to optimize production of these anti-inflammatory terpenes through the modification of culture conditions. An additional goal of this proposal is to test the hypothesis that much of the diversity in the terpenes isolated from gorgonians is due to the biosynthetic capability of symbiotic dinoflagellates. To address this issue, we shall examine the terpene content and biosynthetic capability of dinoflagellate symbionts isolated from selected gorgonians.