News & Events

Warren Vidar

Posted on September 21, 2022


Date - September 21, 2022
1:00 pm - 2:00 pm


Public Ph.D. Defense
Department of Chemistry & Biochemistry
UNC Greensboro
Cech Research Laboratory
Title: Interaction Metabolomics to Discover Synergists in Natural Product Mixtures


Mass spectrometry metabolomics has become increasingly popular as an integral aspect of studies designed to identify active compounds from natural product mixtures. Classical metabolomics data analysis approaches do not consider the possibility that interactions (such as synergy) could occur between mixture components. With this study, we developed “interaction metabolomics” to overcome this limitation. The innovation of interaction metabolomics is the inclusion of compound interaction terms in the data matrix. The interaction terms are calculated as the product of the intensities of each pair of features (detected ions). Herein, we tested the utility of interaction metabolomics by spiking known concentrations of an antimicrobial compound (berberine) and a synergist (piperine) into a set of inactive matrices. We measured the antimicrobial activity for each of the resulting mixtures against Staphylococcus aureus and analyzed the mixtures with liquid chromatography coupled to high-resolution mass spectrometry (LC-MS). When the dataset was processed without compound interaction terms (classical metabolomics), statistical analysis yielded a pattern of false positives, a phenomenon that can be explained by confounding, in this case, due to a left-out interaction in the model. However, interaction metabolomics correctly identified berberine and piperine as the compounds being responsible for synergistic activity. Our results demonstrate the utility of a conceptually new approach for identifying synergists in mixtures that may be useful for applications in natural products research and other areas that require comprehensive mixture analysis.