Targeted isolation and identification of N-N bond-containing bioactive molecules from bacteria
In the modern pharmaceutical industrial, a large number of new drug candidates come from molecules isolated from microbes. These “natural products” include some of our most powerful antibiotics, chemotherapeutics, and other medicines. Unfortunately, investment into natural-product drug discovery has declined since the turn of the century, owing to the high chance of re-discovery of known molecules. However, advances in bioinformatics suggest that the number of potential new drugs available from microbes is enormous. To advance the field of natural product drug discovery and exploit these advances in bioinformatics, we are developing a creative method to discover natural products with specific chemical sub-structures, which have a high probability to become drug candidates. This method is a biosynthetically-inspired, genome-mining technique that employs 15N-NMR as a key technique. Our initial work has resulted in a structurally unprecedented molecule, together with a yet-unknown molecule with exceptional antibiotic activity against gram-negative pathogens. Here we propose to extend our approach for the targeted isolation of additional molecules, followed by assessment of their pharmaceutical properties for preclinical testing.