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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Maximilian J. Helf & Bennett W. Fox & Alexander B. Artyukhin & Ying K. Zhang & Frank C. Schroeder, 2022. "Comparative metabolomics with Metaboseek reveals functions of a conserved fat metabolism pathway in C. elegans," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28391-9
    DOI: 10.1038/s41467-022-28391-9
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    References listed on IDEAS

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    1. Masanori Funabashi & Tyler L. Grove & Min Wang & Yug Varma & Molly E. McFadden & Laura C. Brown & Chunjun Guo & Steven Higginbottom & Steven C. Almo & Michael A. Fischbach, 2020. "A metabolic pathway for bile acid dehydroxylation by the gut microbiome," Nature, Nature, vol. 582(7813), pages 566-570, June.
    2. Michael P. O’Donnell & Bennett W. Fox & Pin-Hao Chao & Frank C. Schroeder & Piali Sengupta, 2020. "A neurotransmitter produced by gut bacteria modulates host sensory behaviour," Nature, Nature, vol. 583(7816), pages 415-420, July.
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    Cited by:

    1. Russell N. Burkhardt & Alexander B. Artyukhin & Erin Z. Aprison & Brian J. Curtis & Bennett W. Fox & Andreas H. Ludewig & Diana Fajardo Palomino & Jintao Luo & Amaresh Chaturbedi & Oishika Panda & Che, 2023. "Sex-specificity of the C. elegans metabolome," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Tae Hyung Won & Jin Woo Bok & Nischala Nadig & Nandhitha Venkatesh & Grant Nickles & Claudio Greco & Fang Yun Lim & Jennifer B. González & B. Gillian Turgeon & Nancy P. Keller & Frank C. Schroeder, 2022. "Copper starvation induces antimicrobial isocyanide integrated into two distinct biosynthetic pathways in fungi," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Bennett W. Fox & Maximilian J. Helf & Russell N. Burkhardt & Alexander B. Artyukhin & Brian J. Curtis & Diana Fajardo Palomino & Allen F. Schroeder & Amaresh Chaturbedi & Arnaud Tauffenberger & Cheste, 2024. "Evolutionarily related host and microbial pathways regulate fat desaturation in C. elegans," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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