Presentation description
Bacterial natural products (NPs) are a key source of therapeutically relevant compounds; over half of all approved drugs between 1981 and 2019 are NPs or NP-derived. Amidst a global antimicrobial resistance crisis, it is critical that we continue to search for novel NPs. A promising and rich source of these novel scaffolds are underexplored bacterial species that, due to their challenging growth requirements, were neglected during the golden age of NP discovery. Methane-oxidizing bacteria (methanotrophs) are one such example. Methanotrophs use methane as their sole source of carbon and energy and have great biosynthetic potential. We have identified a biosynthetic gene cluster (BGC) in the methanotroph Methylobacter tundripaludum strain 21/22 (21/22) that is predicted to produce a cytotoxic microsclerodermin derivative. Using genetic tools developed in our lab, we were able to link this BGC with the predicted microsclerodermin derivative, microsclerodermin H (MscH). We have confirmed that this compound possesses anti-fungal activity against Saccharomyces cerevisiae (brewer's yeast). This BGC is unique as the MscH biosynthetic genes are bisected by a different BGC responsible for producing a novel natural product. We hypothesize that the novel compound works synergistically with MscH to modulate bioactivity. We have purified and begun characterizing this novel compound using high-resolution mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. In continuing work, we will complete a full structural elucidation of this compound and investigate its biological function. NPs develop under intense selective pressure making them highly specific for their targets. Thus, this pair of compounds has the potential to be a useful and potent anti-fungal/anti-tumor scaffold.