UC San Diego

Recently, there has been remarkable interest in mining the chemical diversity in specialized metabolites scaffolds to identify novel molecules with altered bioactivity from natural source. Here, we present the use of MS/MS networking guided comparative metabolomics to profile sequenced and unsequenced bacteria. This enables the dereplication of known specialized metabolites as well as the discovery of new analogs that are produced in an environmental unsequenced bacterium Streptomyces sp. DSM5940 by comparing the metabolic output with a sequenced bacterium Streptomyces roseosporus. The following differential comparison of gene cluster profiling, MS/MS and 2D NMR greatly accelerates the structure elucidation process, allowing us to rapidly identify an analog of the stenothricins in which a lysine is changed to a serine, which we have named stenothrisercin. The finally cytological profiling indicates lysine may be an essential structural motif for the antimicrobial activity. Our study demonstrates MS/MS networking, along with differential comparison significantly accelerates the process of mining new natural product analogs