Expanding the Metabolome with Applications in Neuroscience and Bioremediation

The study of small molecules, while not a new concept, is still at its infancy for both detection and structure identification. My work at the University of Tennessee, Knoxville has been focused on the advancement of both analytical detection and identification of novel compounds as potential small molecule targets. Using in vitro and in vivo neurometabolomics on rodents as my foundation, I have been able to identify numerous small molecules for further study in the areas of social defeat stress and across various states of consciousness. Through untargeted metabolomics via liquid chromatography coupled with high-resolution mass spectrometry, this research has provided the additional hurdle of identifying novel targets among the unidentified spectral features, or “unknown” metabolites. In the final chapter of this dissertation, I emphasize my ability to elucidate the structure of a novel cobamide identified as a native prosthetic group in catalytically active tetrachloroethene reductive dehalogenases of Desulfobacterium hafniense. Utilizing stable isotope labeling of microbial cultures, mass spectrometry confirmed the molecular formula, followed by 1D and 2D nuclear magnetic resonance spectroscopy to characterize structural connectivity. The research presented in this dissertation advances the field of novel compound discovery and characterization for the identification of small molecule targets by highlighting unique research within the fields of neurometabolomics and microbiology.