Utilizing Understudied Bacteria in the Pursuit of Natural Products Drug Discovery

For decades natural products have been a leading source of bioactive compounds that have had a profound impact on human health through their development into clinical pharmaceuticals. However, the private sector has moved away from this pursuit. This divestment of microbial drug discovery can be attributed to several factors, the most common being: i) continued rediscovery of known chemical entities, and ii) a move towards small molecules generated through combinatorial chemistry and high throughput screening (HTS). Nonetheless, academic researchers continued to see the promise of bacterial secondary metabolites with advances in genomics and metabolomics, suggesting that the microbial world still encodes for a reservoir of yet described chemical entities. We opine that the field must move towards the direction of targeting understudied bacterial phyla or understudied bacterial genera within well investigated phyla to access this new chemical space. Herein we describe a novel mass spectrometry pipeline to achieve this. We assert that using MALDI MS and IDBac in the front end of discovery programs will afford researchers an inexpensive, rapid, and precise method to mine large environmental collections of isolates for understudied or target bacteria. While then investigating an understudied bacterial isolate Chitinophaga AC21 to demonstrate the promise that understudied bacteria show for natural products drug discovery.