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J Am Chem Soc. 2018 Feb 28;140(8):2841-2852. doi: 10.1021/jacs.7b11811. Epub 2018 Feb 16.

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

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Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14850, United States.
Division of Biology and Biological Engineering, California Institute of Technology , Pasadena, California 91125, United States.


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.

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