Journal Article

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

Artyukhin, Alexander B., Zhang, Ying K., Fox, Bennett W., Schroeder, Frank C., Helf, Maximilian J.

2022

Overview

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. Untargeted mass spectrometry-based metabolomics can reveal new biochemistry, but data analysis is challenging. Here, the authors develop Metaboseek, an open-source software that facilitates metabolite discovery, and apply it to characterize fatty acid alpha-oxidation in C. elegans .

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 140/131 / 140/58 / 631/114/1314 / 631/1647/296 / 631/443/319/320 / 631/45/287/1183 / 64/11 / Animals / Annotations / Caenorhabditis elegans - genetics / Caenorhabditis elegans - metabolism / Carbon-Carbon Lyases - genetics / Carbon-Carbon Lyases - metabolism / Cyclopropane / Data analysis / Fat metabolism / Fatty acids / Fatty Acids - genetics / Fatty Acids - metabolism / Humanities and Social Sciences / Humans / Larva / Lipid metabolism / Lipid Metabolism - genetics / Lipids / Mass Spectrometry / Mass spectroscopy / Metabolic Networks and Pathways - genetics / Metabolic pathways / Metabolism / Metabolites / Metabolome / Metabolomics / Metabolomics - methods / multidisciplinary / Oxidation / Oxidation-Reduction / Science / Science (multidisciplinary) / Scientific imaging / Spectroscopy / Statistical analysis / Worms