Investigator: Matthew Bertin, University of Rhode Island

Scientific Theme: Cancer

Abstract:  Natural products have been an extraordinary source of chemotherapeutic lead compounds and serve an important inspirational role in the development of new synthetic therapeutics. Marine cyanobacteria are ancient organisms with a long evolutionary history that has optimized their ability to generate chemical substances with structural diversity and biological target specificity. As a result, marine cyanobacteria have been a remarkable source of anti-cancer lead compounds. The marine cyanobacterium Trichodesmium thiebautii has largely been overlooked as a potential producer of secondary metabolites due to an inability to establish uni-algal cultures. Our laboratory has obtained material from an environmental Trichodesmium thiebautii bloom that occurred in the Gulf of Mexico in 2014. In our preliminary studies, bioassay-guided fractionation of this bloom material has resulted in the isolation of five new structurally diverse polyketide and hybrid peptide-polyketide molecules. These molecules show structural similarity to known chemical entities with anti-cancer properties. While the bloom is dominated by T. thiebautii, it represents a complex collection of microorganisms in a highly competitive environment. This competition for space and resources should result in chemical adaptations by the microbes in the form of small bioactive molecules and our over-arching goal is to demonstrate that environmental Trichodesmium blooms are reservoirs of unique chemical entities that can be developed into anti-cancer lead compounds. The specific aims which will accomplish this goal are: 1) to complete the full structure characterization, including absolute configuration analysis, of the five new structurally diverse metabolites we have isolated from this Trichodesmium sample and 2) to evaluate the cytotoxic potency of these five new metabolites against human colon cancer cells (HCT-116) and human lung cancer cells (H460) using cell viability assays. Structures will be characterized using spectroscopic techniques and chemical derivative formation. In vitro viability assays using multiple human cancer cell lines with be used to determine the potency of the isolated compounds. Compounds showing potent cytotoxicity will continue to be evaluated as chemotherapeutic lead molecules in further studies. The results of this project should allow for future direct chemical investigations of Trichodesmium blooms from diverse geographic areas searching for unique metabolites with anti-cancer properties.

Human Health Relevance:  Natural compounds have been an essential source of new chemotherapeutic leads. This project investigates the diverse chemical components in an environmental cyanobacteria bloom in order to identify and ultimately develop new anti-cancer lead molecules.