LC/MS Untargeted Metabolomics for Prioritizing Marine Invertebrate-Associated Bacteria for Discovery of Natural Products

We are focusing on diverse, marine invertebrate-associated bacteria from which to discover new natural products. A key obstacle plaguing the discovery of novel natural products is the high incidence of rediscovery of known compounds. To alleviate this obstacle, we are employing LC/MS untargeted metabolomics profiling to quickly prioritize strains biosynthesizing putatively novel compounds for in-depth study and/or for placing in screening libraries.

Principal component analysis (PCA) takes the data-rich LC/MS analyses of bacterial strain metabolites and groups the analyses according to variance. This allows us to rapidly identify strains which vary the most from other strains and putatively dereplicate their unique compounds. Through both traditional natural products isolation approaches and the LC/MS-PCA prioritization approach, we are discovering many novel natural products, including Bottromycin D, which is an anti-methicillin resistant Staphylococcus aureus (anti-MRSA) compound. We are currently exploring ways to expand upon this LC/MS untargeted metabolomics approach to further expedite natural product drug discovery.