1. Biochemistry and Chemical Biology
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Modular metabolite assembly in C. elegans depends on carboxylesterases and formation of lysosome-related organelles

  1. Henry H Le
  2. Chester JJ Wrobel
  3. Sarah M Cohen
  4. Jingfang Yu
  5. Heenam Park
  6. Maximilian J Helf
  7. Brian J Curtis
  8. Joseph C Kruempel
  9. Pedro Reis Rodrigues
  10. Patrick J Hu
  11. Paul W Sternberg  Is a corresponding author
  12. Frank C Schroeder  Is a corresponding author
  1. BTI/Cornell University, United States
  2. Caltech, United States
  3. University of Michigan Medical School, United States
  4. Vanderbilt University School of Medicine, United States
  5. Howard Hughes Medical Institute, California Institute of Technology, United States
Research Article
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Cite this article as: eLife 2020;9:e61886 doi: 10.7554/eLife.61886

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.

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Author details

  1. Henry H Le

    Chemistry and Chemical Biology, BTI/Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2942-2357
  2. Chester JJ Wrobel

    Chemistry and Chemical Biology, BTI/Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sarah M Cohen

    Division of Biology and Biological Engineering, Caltech, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jingfang Yu

    Chemistry and Chemical Biology, BTI/Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1770-5368
  5. Heenam Park

    Division of Biology and Biological Engineering, Caltech, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Maximilian J Helf

    Chemistry and Chemical Biology, BTI/Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Brian J Curtis

    Chemistry and Chemical Biology, BTI/Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Joseph C Kruempel

    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Pedro Reis Rodrigues

    Chemistry and Chemical Biology, BTI/Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Patrick J Hu

    Departments of Medicine and Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Paul W Sternberg

    Division of Biology & BIological Engineering, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United States
    For correspondence
    pws@caltech.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7699-0173
  12. Frank C Schroeder

    Chemistry and Chemical Biology, BTI/Cornell University, Ithaca, United States
    For correspondence
    fs31@cornell.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4420-0237

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

  1. Michael A Marletta, University of California, Berkeley, United States

Publication history

  1. Received: August 7, 2020
  2. Accepted: October 14, 2020
  3. Accepted Manuscript published: October 16, 2020 (version 1)

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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