1. Biochemistry and Chemical Biology
  2. Microbiology and Infectious Disease
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Rhodoquinone biosynthesis in C.elegans requires precursors generated by the kynurenine pathway

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Cite this article as: eLife 2019;8:e48165 doi: 10.7554/eLife.48165

Abstract

Parasitic helminths infect over a billion humans. To survive in the low oxygen environment of their hosts, these parasites use unusual anaerobic metabolism - this requires rhodoquinone (RQ), an electron carrier that is made by very few animal species. Crucially RQ is not made or used by any parasitic hosts and RQ synthesis is thus an ideal target for anthelmintics. However, little is known about how RQ is made and no drugs are known to block RQ synthesis. C.elegans makes RQ and can use RQ-dependent metabolic pathways - here, we use C.elegans genetics to show that tryptophan degradation via the kynurenine pathway is required to generate the key amine-containing precursors for RQ synthesis. We show that C.elegans requires RQ for survival in hypoxic conditions and, finally, we establish a high throughput assay for drugs that block RQ-dependent metabolism. This may drive the development of a new class of anthelmintic drugs. This study is a key first step in understanding how RQ is made in parasitic helminths.

Article and author information

Author details

  1. Samantha Del Borrello

    The Donnelly Centre, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0117-0592
  2. Margot Lautens

    The Donnelly Centre, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8503-9603
  3. Kathleen Dolan

    The Donnelly Centre, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. June H Tan

    The Donnelly Centre, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6597-3952
  5. Taylor Davie

    The Donnelly Centre, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Michael R Schertzberg

    The Donnelly Centre, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Mark A Spensley

    The Donnelly Centre, University of Toronto, Toronto, Canada
    For correspondence
    maspensley@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6167-4461
  8. Amy A Caudy

    The Donnelly Centre, University of Toronto, Toronto, Canada
    For correspondence
    amy.caudy@utoronto.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6307-8137
  9. Andrew G Fraser

    The Donnelly Centre, University of Toronto, Toronto, Canada
    For correspondence
    andyfraser.utoronto@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9939-6014

Funding

Canadian Institutes of Health Research (501584)

  • Andrew G Fraser

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Phillip A Newmark, HHMI/Morgridge Institute for Research, University of Wisconsin-Madison, United States

Publication history

  1. Received: May 2, 2019
  2. Accepted: June 22, 2019
  3. Accepted Manuscript published: June 24, 2019 (version 1)

Copyright

© 2019, Del Borrello 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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