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Published February 28, 2018 | public
Journal Article Open

Metabolomic "Dark Matter" Dependent on Peroxisomal β-Oxidation in Caenorhabditis elegans


Peroxisomal β-oxidation (pβo) is a highly conserved fat metabolism pathway involved in the biosynthesis of diverse signaling molecules in animals and plants. In Caenorhabditis elegans, pβo is required for the biosynthesis of the ascarosides, signaling molecules that control development, lifespan, and behavior in this model organism. Via comparative mass spectrometric analysis of pβo mutants and wildtype, we show that pβo in C. elegans and the satellite model P. pacificus contributes to life stage-specific biosynthesis of several hundred previously unknown metabolites. The pβo-dependent portion of the metabolome is unexpectedly diverse, e.g., intersecting with nucleoside and neurotransmitter metabolism. Cell type-specific restoration of pβo in pβo-defective mutants further revealed that pβo-dependent submetabolomes differ between tissues. These results suggest that interactions of fat, nucleoside, and other primary metabolism pathways can generate structural diversity reminiscent of that arising from combinatorial strategies in microbial natural product biosynthesis.

Additional Information

© 2018 American Chemical Society. Received 8 November 2017. Published online 5 February 2018. We are grateful to David Kiemle for help with acquiring NMR spectra. This work was supported in part by the NIH (GM113692, GM088290 to FCS, and T32GM007616 to A.E.A.) and HHMI.

Attached Files

Supplemental Material - ja7b11811_si_001.pdf

Supplemental Material - ja7b11811_si_002.xlsx

Supplemental Material - ja7b11811_si_003.xlsx

Accepted Version - nihms953485.pdf


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August 19, 2023
August 19, 2023