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Exploring host-microbiota co-metabolism – New chemical biology tools for metabolomics analysis
Daniel Globisch, PhD
Uppsala University

One of the most exciting scientific developments in the past decade has been the understanding that gut microbiota profoundly impact human physiology. The complex consortium of trillions of microbes possesses a wide range of metabolic activity. This metabolic interspecies communication represents a tremendous opportunity for the discovery of unknown bioactive molecules as only limited information on this co-metabolism has been elucidated on a molecular level. Mass spectrometry-based metabolomics analysis is the method of choice for the analysis of known and discovery of unknown metabolites. Chemical Biology tools are still limited in metabolomics compared to other ‘omics research fields. Especially, the detailed and selective analysis of microbial metabolism remains a major challenge that requires specific techniques.

We have developed new state-of-the-art Chemical Biology methodologies for that exceed the scope of global metabolomics analysis. These unique metabolite analysis tools overcome limitations in metabolomics and were applied for the discovery of unknown metabolites in human samples to evaluate their potential as biomarkers. We have developed arylsulfatase-based metabolite analysis methods for specific identification of sulfated metabolites as this compound class represents a signature for microbiome-host co-metabolism. This analysis led to identification of more than 230 sulfated metabolites, exceeding the number of this metabolite class in common metabolomics databases. An optimized enzymatic method was applied for a dietary intervention study to investigate the dietary sulfatome. Several previously unknown and undetected metabolites are derived from specific microbiota metabolism. Based on our interested in phase II modifications, we identified a series of unexpected substrates for the common human N-acetyltransferase NAT2. Furthermore, we have also designed unique chemoselective probes immobilized

Aug 25, 2021 10:00 AM in Pacific Time (US and Canada)

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