Modular metabolite assembly in C. elegans depends on carboxylesterases and formation of lysosome-related organelles
- BTI/Cornell University, United States
- Caltech, United States
- University of Michigan Medical School, United States
- Vanderbilt University School of Medicine, United States
- Howard Hughes Medical Institute, California Institute of Technology, United States
Abstract
Signaling molecules derived from attachment of diverse metabolic building blocks to ascarosides play a central role in the life history of C. elegans and other nematodes; however, many aspects of their biogenesis remain unclear. Using comparative metabolomics, we show that a pathway mediating formation of intestinal lysosome-related organelles (LROs) is required for biosynthesis of most modular ascarosides as well as previously undescribed modular glucosides. Similar to modular ascarosides, the modular glucosides are derived from highly selective assembly of moieties from nucleoside, amino acid, neurotransmitter, and lipid metabolism, suggesting that modular glucosides, like the ascarosides, may serve signaling functions. We further show that carboxylesterases that localize to intestinal organelles are required for the assembly of both modular ascarosides and glucosides via ester and amide linkages. Further exploration of LRO function and carboxylesterase homologs in C. elegans and other animals may reveal additional new compound families and signaling paradigms.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. MS/MS data is available via MassIVE under accession number: MSV000086293.
Article and author information
Author details
Funding
National Institutes of Health (R35 GM131877)
- Frank C Schroeder
National Institutes of Health (R24 OD023041)
- Paul W Sternberg
National Institutes of Health (5T32GM008500)
- Brian J Curtis
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Michael A Marletta, University of California, Berkeley, United States
Version history
- Received: August 7, 2020
- Accepted: October 14, 2020
- Accepted Manuscript published: October 16, 2020 (version 1)
- Version of Record published: November 4, 2020 (version 2)
Copyright
© 2020, Le et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Modular metabolite assembly in C. elegans depends on carboxylesterases and formation of lysosome-related organelles
eLife 9:e61886.
https://doi.org/10.7554/eLife.61886
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