This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The abundance of drug-resistant bacterial infections and cancers has generated an urgent interest in the search for prototype antibiotic and anticancer leads. Oceans nearly possess 80% of Earth's animal life. The chemical and biological diversity of marine natural products make them an enormous resource of unique and highly bioactive compounds. Studies suggest that many bioactive compounds isolated from marine invertebrates such as sponges, coelenterates, mollusks, or protochordates, are truly originating from symbiotic microorganisms, e.g., bacteria, fungi, blue green algae, dinoflagellates, or haptophytes. Marine microorganisms are the most diverse and renewable resources of new compounds, which are very likely to have biological activity including anticancer or antiinfective effects. Most of marine microorganisms live symbiotically in other soft-bodied marine organisms, which lack obvious structural defenses. This study will explore the ability of cultured microorganisms to produce latrunculins, sipholanes, cembranoids, and any related anticancer/anti-infective secondary metabolites. Hypothesis of this proposal is: bioactive natural products are produced by symbiotic microorganisms associated with the Red Sea sponge N. magnifica, and S. siphonella, and the soft coral S. glaucum. These compounds can be produced on large scale by in vitro culturing of their source microorganisms. This hypothesis will be tested by pursuing the following specific aims: 1- Isolation/identification of symbiotic microorganisms associated with the aforementioned animals. 2- Large-scale culturing of the isolated microorganism and testing their extracts for latrunculins, sipholanes, cembranoids, and other novel secondary metabolites. 3- Evaluation of anticancer and antibiotic activity of the extracts and isolated compounds.
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