LCMS-Based Metabolomics to Stimulate Natural Products Drug Discovery from Marine Invertebrate Associated Actinobacteria

Mass spectrometry continues to evolve at a rapid pace providing enabling technologies to stimulate natural products drug discovery. We have shown that marine bacteria can be rapidly investigated using principal component analysis (PCA) of LCMS data.¹ These methods have led to a high discovery rate of new and novel natural products including a novel antifungal agent with in vivo efficacy. Additionally, these tools can be more broadly applied to the study of biological problems that are encountered in a bacterial drug discovery environment including optimizing production, optimizing chemical diversity, and investigating interspecies interactions. We have now tied these up front metabolomics methods into a new approach for creating natural product libraries. This new approach to library generation facilitates rapid NMR characterization of hits identified through screening programs. A summary of these methods and the resulting discoveries will be presented.

1. Hou, Y.; Braun, D. R.; Michel, C. R.; Klassen, J. L.; Adnani, N.; Wyche, T. P.; Bugni, T. S. Microbial Strain Prioritization Using Metabolomics Tools for the Discovery of Natural Products. Anal. Chem. 2012, 84, 4277 – 4283, PMID: 22519562.