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Native Metabolomics Talk ASMS 2021
>> YOUR LINK HERE: ___ http://youtube.com/watch?v=jGMDA3craqc
Recording from our Native Metabolomics talk at the ASMS conference 2021 in Philadelphia. • A prep-print of the manuscript describing the work can be found here: https://www.biorxiv.org/content/10.11... • Talk Abstract: • Native Metabolomics - High-Throughput Screening of Protein-Metabolite Binding from Crude Extracts in the Mass Spectrometer • Raphael Reher1, 2; Allegra Aron3; Pavla Fajtova3; Pieter C. Dorrestein3; Anthony O'donoghue3; William H Gerwick2, 3; Daniel Petras3, 4 • 1: University of Halle-Wittenberg, Halle (Saale), Germany • 2: Scripps Institution of Oceanography, La Jolla, USA • 3: Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, La Jolla, USA • 4: CMFI Cluster of Excellence, Interfaculty Institute of Microbiology and Medicine, University of Tuebingen, Tuebingen, Germany • Introduction • The diversity of natural products within microbial communities represent a fascinating source of chemical entities that are fundamentally important for ecosystem function. Thanks to recent advances in tandem mass spectrometry, we can create highly resolved inventories of small molecules in diverse environments. However, the biological activities of most natural products and metabolites remain unknown. Traditionally, separation of extracts, structural characterization and bioactivity determination are independent processes. Here we demonstrate an native metabolomics approach that integrates separation, compound annotation and simultaneous screening for bioactivity properties. • Methods • In this approach, we coupled liquid chromatography tandem mass spectrometry-based metabolomics with online native protein infusion mass spectrometry, in combination with molecular networking, to screen an extract from an environmental cyanobacteria community for protease inhibitors. • Preliminary Data • Applying our approach to environmental cyanobacterial crude extracts, we identified 30 cyclodepsipeptides as putative chymotrypsin binders from the extract pool. Mass spectrometry directed purification of the six most prevalent compounds enabled full structure elucidation via nuclear magnetic resonance spectroscopy, empirically identifying a family of serine protease inhibitors with nanomolar potency. • Novel Aspect • Native metabolomics enables the screening of small molecule-protein binding directly from crude extracts.
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