CaltechAUTHORS
  A Caltech Library Service

Modular metabolite assembly in Caenorhabditis elegans depends on carboxylesterases and formation of lysosome-related organelles

Le, Henry H. and Wrobel, Chester J. J. and Cohen, Sarah M. and Yu, Jingfang and Park, Heenam and Helf, Maximilian J. and Curtis, Brian J. and Kruempel, Joseph C. and Reis-Rodrigues, Pedro and Hu, Patrick J. and Sternberg, Paul W. and Schroeder, Frank C. (2020) Modular metabolite assembly in Caenorhabditis elegans depends on carboxylesterases and formation of lysosome-related organelles. eLife, 2020 (9). Art. No. e61886. ISSN 2050-084X. PMCID PMC7641594. https://resolver.caltech.edu/CaltechAUTHORS:20201013-104022895

[img] PDF - Published Version
Creative Commons Attribution.

3196Kb
[img]
Preview
PDF - Accepted Version
Creative Commons Attribution.

45Mb
[img] PDF - Submitted Version
See Usage Policy.

3848Kb
[img] Archive (ZIP) - Supplemental Material
Creative Commons Attribution.

29Mb
[img] PDF (NMR spectra appendix) - Supplemental Material
Creative Commons Attribution.

1047Kb
[img] MS Word (Transparent reporting form) - Supplemental Material
Creative Commons Attribution.

248Kb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20201013-104022895

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.7554/eLife.61886DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7641594/PubMed CentralArticle
https://doi.org/10.1101/2020.08.22.262956DOIDiscussion Paper
ORCID:
AuthorORCID
Le, Henry H.0000-0003-2942-2357
Wrobel, Chester J. J.0000-0001-6047-4644
Cohen, Sarah M.0000-0002-5233-2280
Yu, Jingfang0000-0003-1770-5368
Park, Heenam0000-0001-7911-5828
Helf, Maximilian J.0000-0002-1393-3999
Sternberg, Paul W.0000-0002-7699-0173
Schroeder, Frank C.0000-0002-4420-0237
Alternate Title:Modular metabolite assembly in C. elegans depends on carboxylesterases and formation of lysosome-related organelles
Additional Information:© 2020 Le et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Received: 07 August 2020; Accepted: 14 October 2020; Published: 16 October 2020. This research was funded by an NIH Chemical Biology Interface (CBI) Training Grant 5T32GM008500 (to B.C.), National Institutes of Health grants R35 GM131877 (to F.C.S.), and R24OD023041 (to P.W. S.). F.C.S. is a Faculty Scholar of the Howard Hughes Medical Institute. We thank WormBase for sequences, Tsui-Fen Chou for Cas9 protein, Ying (Kitty) Zhang for assistance with NMR spectroscopy, and Navid Movahed for assistance with mass spectrometry. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Author contributions: Henry H Le, Chester JJ Wrobel, Conceptualization, Data curation, Formal analysis, Investigation, Writing - original draft, Writing - review and editing; Sarah M Cohen, Conceptualization, Resources, Methodology; Jingfang Yu, Resources, Formal analysis; Heenam Park, Resources, Methodology; Maximilian J Helf, Software, Methodology; Brian J Curtis, Resources, Investigation; Joseph C Kruempel, Patrick J Hu, Resources; Pedro Reis Rodrigues, Data curation, Investigation; Paul W Sternberg, Conceptualization, Funding acquisition, Writing - original draft, Project administration, Writing - review and editing; Frank C Schroeder, Conceptualization, Formal analysis, Supervision, Funding acquisition, Writing - original draft, Project administration, Writing - review and editing. 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.
Funders:
Funding AgencyGrant Number
NIH Predoctoral Fellowship5T32GM008500
NIHR35 GM131877
NIHR24OD023041
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:9
PubMed Central ID:PMC7641594
Record Number:CaltechAUTHORS:20201013-104022895
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201013-104022895
Official Citation:Modular metabolite assembly in Caenorhabditis elegans depends on carboxylesterases and formation of lysosome-related organelles. Le, Wrobel, et al. eLife 2020;9:e61886. DOI: https://doi.org/10.7554/eLife.61886
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106016
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:13 Oct 2020 18:01
Last Modified:24 Nov 2020 17:55

Repository Staff Only: item control page