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Rhodoquinone biosynthesis in C. elegans requires precursors generated by the kynurenine pathway
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 parasiti...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656428/ https://www.ncbi.nlm.nih.gov/pubmed/31232688 http://dx.doi.org/10.7554/eLife.48165 |
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author | Del Borrello, Samantha Lautens, Margot Dolan, Kathleen Tan, June H Davie, Taylor Schertzberg, Michael R Spensley, Mark A Caudy, Amy A Fraser, Andrew G |
author_facet | Del Borrello, Samantha Lautens, Margot Dolan, Kathleen Tan, June H Davie, Taylor Schertzberg, Michael R Spensley, Mark A Caudy, Amy A Fraser, Andrew G |
author_sort | Del Borrello, Samantha |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6656428 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-66564282019-07-25 Rhodoquinone biosynthesis in C. elegans requires precursors generated by the kynurenine pathway Del Borrello, Samantha Lautens, Margot Dolan, Kathleen Tan, June H Davie, Taylor Schertzberg, Michael R Spensley, Mark A Caudy, Amy A Fraser, Andrew G eLife Biochemistry and Chemical Biology 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. eLife Sciences Publications, Ltd 2019-06-24 /pmc/articles/PMC6656428/ /pubmed/31232688 http://dx.doi.org/10.7554/eLife.48165 Text en © 2019, Del Borrello et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry and Chemical Biology Del Borrello, Samantha Lautens, Margot Dolan, Kathleen Tan, June H Davie, Taylor Schertzberg, Michael R Spensley, Mark A Caudy, Amy A Fraser, Andrew G Rhodoquinone biosynthesis in C. elegans requires precursors generated by the kynurenine pathway |
title | Rhodoquinone biosynthesis in C. elegans requires precursors generated by the kynurenine pathway |
title_full | Rhodoquinone biosynthesis in C. elegans requires precursors generated by the kynurenine pathway |
title_fullStr | Rhodoquinone biosynthesis in C. elegans requires precursors generated by the kynurenine pathway |
title_full_unstemmed | Rhodoquinone biosynthesis in C. elegans requires precursors generated by the kynurenine pathway |
title_short | Rhodoquinone biosynthesis in C. elegans requires precursors generated by the kynurenine pathway |
title_sort | rhodoquinone biosynthesis in c. elegans requires precursors generated by the kynurenine pathway |
topic | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656428/ https://www.ncbi.nlm.nih.gov/pubmed/31232688 http://dx.doi.org/10.7554/eLife.48165 |
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