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Elife. 2019 Jun 24;8. pii: e48165. doi: 10.7554/eLife.48165.

Rhodoquinone biosynthesis in C. elegans requires precursors generated by the kynurenine pathway.

Author information

1
The Donnelly Centre, University of Toronto, Toronto, Canada.
2
Whole Animal Phenotyping, Phenalysys Inc, Toronto, Canada.
#
Contributed equally

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.

KEYWORDS:

C. elegans; anaerobic metabolism; biochemistry; chemical biology; global health; infectious disease; microbiology; parasitic helminth; rhodoquinone

Conflict of interest statement

SD, ML, KD, JT, TD, MS, AC, AF No competing interests declared, MS Affiliated with Phenalysys Inc. The author has no other competing interests to declare

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