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Comparative metabolomics with Metaboseek reveals functions of a conserved fat metabolism pathway in C. elegans

Maximilian J. Helf, Bennett W. Fox, Alexander B. Artyukhin, Ying K. Zhang and Frank C. Schroeder ()
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Maximilian J. Helf: Cornell University
Bennett W. Fox: Cornell University
Alexander B. Artyukhin: State University of New York
Ying K. Zhang: Cornell University
Frank C. Schroeder: Cornell University

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract Untargeted metabolomics via high-resolution mass spectrometry can reveal more than 100,000 molecular features in a single sample, many of which may represent unidentified metabolites, posing significant challenges to data analysis. We here introduce Metaboseek, an open-source analysis platform designed for untargeted comparative metabolomics and demonstrate its utility by uncovering biosynthetic functions of a conserved fat metabolism pathway, α-oxidation, using C. elegans as a model. Metaboseek integrates modules for molecular feature detection, statistics, molecular formula prediction, and fragmentation analysis, which uncovers more than 200 previously uncharacterized α-oxidation-dependent metabolites in an untargeted comparison of wildtype and α-oxidation-defective hacl-1 mutants. The identified metabolites support the predicted enzymatic function of HACL-1 and reveal that α-oxidation participates in metabolism of endogenous β-methyl-branched fatty acids and food-derived cyclopropane lipids. Our results showcase compound discovery and feature annotation at scale via untargeted comparative metabolomics applied to a conserved primary metabolic pathway and suggest a model for the metabolism of cyclopropane lipids.

Date: 2022
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DOI: 10.1038/s41467-022-28391-9

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