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

Artyukhin, Alexander B. and Zhang, Ying K. and Akagi, Allison E. and Panda, Oishika and Sternberg, Paul W. and Schroeder, Frank C. (2018) Metabolomic “Dark Matter” Dependent on Peroxisomal β-Oxidation in Caenorhabditis elegans. Journal of the American Chemical Society, 140 (8). pp. 2841-2852. ISSN 0002-7863. PMCID PMC5890438. http://resolver.caltech.edu/CaltechAUTHORS:20180220-093417995

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/jacs.7b11811DOIArticle
https://pubs.acs.org/doi/abs/10.1021/jacs.7b11811PublisherArticle
https://pubs.acs.org/doi/suppl/10.1021/jacs.7b11811PublisherSupporting Information
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890438PubMed CentralArticle
ORCID:
AuthorORCID
Akagi, Allison E.0000-0002-7233-6190
Sternberg, Paul W.0000-0002-7699-0173
Schroeder, Frank C.0000-0002-4420-0237
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.
Funders:
Funding AgencyGrant Number
NIHGM113692
NIHGM088290
NIH Predoctoral FellowshipT32GM007616
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
PubMed Central ID:PMC5890438
Record Number:CaltechAUTHORS:20180220-093417995
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20180220-093417995
Official Citation:Metabolomic “Dark Matter” Dependent on Peroxisomal β-Oxidation in Caenorhabditis elegans. Alexander B. Artyukhin, Ying K. Zhang, Allison E. Akagi, Oishika Panda, Paul W. Sternberg, and Frank C. Schroeder. Journal of the American Chemical Society 2018 140 (8), 2841-2852. DOI: 10.1021/jacs.7b11811
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:84888
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:22 Feb 2018 04:46
Last Modified:06 May 2019 20:24

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