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Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets
The Apicomplexa phylum comprises thousands of distinct intracellular parasite species, including coccidians, haemosporidians, piroplasms, and cryptosporidia. These parasites are characterized by complex and divergent life cycles occupying a variety of host niches. Consequently, they exhibit distinct...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8717973/ https://www.ncbi.nlm.nih.gov/pubmed/34969059 http://dx.doi.org/10.1371/journal.ppat.1010124 |
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author | de Vries, Laura E. Lunghi, Matteo Krishnan, Aarti Kooij, Taco W. A. Soldati-Favre, Dominique |
author_facet | de Vries, Laura E. Lunghi, Matteo Krishnan, Aarti Kooij, Taco W. A. Soldati-Favre, Dominique |
author_sort | de Vries, Laura E. |
collection | PubMed |
description | The Apicomplexa phylum comprises thousands of distinct intracellular parasite species, including coccidians, haemosporidians, piroplasms, and cryptosporidia. These parasites are characterized by complex and divergent life cycles occupying a variety of host niches. Consequently, they exhibit distinct adaptations to the differences in nutritional availabilities, either relying on biosynthetic pathways or by salvaging metabolites from their host. Pantothenate (Pan, vitamin B5) is the precursor for the synthesis of an essential cofactor, coenzyme A (CoA), but among the apicomplexans, only the coccidian subgroup has the ability to synthesize Pan. While the pathway to synthesize CoA from Pan is largely conserved across all branches of life, there are differences in the redundancy of enzymes and possible alternative pathways to generate CoA from Pan. Impeding the scavenge of Pan and synthesis of Pan and CoA have been long recognized as potential targets for antimicrobial drug development, but in order to fully exploit these critical pathways, it is important to understand such differences. Recently, a potent class of pantothenamides (PanAms), Pan analogs, which target CoA-utilizing enzymes, has entered antimalarial preclinical development. The potential of PanAms to target multiple downstream pathways make them a promising compound class as broad antiparasitic drugs against other apicomplexans. In this review, we summarize the recent advances in understanding the Pan and CoA biosynthesis pathways, and the suitability of these pathways as drug targets in Apicomplexa, with a particular focus on the cyst-forming coccidian, Toxoplasma gondii, and the haemosporidian, Plasmodium falciparum. |
format | Online Article Text |
id | pubmed-8717973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-87179732021-12-31 Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets de Vries, Laura E. Lunghi, Matteo Krishnan, Aarti Kooij, Taco W. A. Soldati-Favre, Dominique PLoS Pathog Review The Apicomplexa phylum comprises thousands of distinct intracellular parasite species, including coccidians, haemosporidians, piroplasms, and cryptosporidia. These parasites are characterized by complex and divergent life cycles occupying a variety of host niches. Consequently, they exhibit distinct adaptations to the differences in nutritional availabilities, either relying on biosynthetic pathways or by salvaging metabolites from their host. Pantothenate (Pan, vitamin B5) is the precursor for the synthesis of an essential cofactor, coenzyme A (CoA), but among the apicomplexans, only the coccidian subgroup has the ability to synthesize Pan. While the pathway to synthesize CoA from Pan is largely conserved across all branches of life, there are differences in the redundancy of enzymes and possible alternative pathways to generate CoA from Pan. Impeding the scavenge of Pan and synthesis of Pan and CoA have been long recognized as potential targets for antimicrobial drug development, but in order to fully exploit these critical pathways, it is important to understand such differences. Recently, a potent class of pantothenamides (PanAms), Pan analogs, which target CoA-utilizing enzymes, has entered antimalarial preclinical development. The potential of PanAms to target multiple downstream pathways make them a promising compound class as broad antiparasitic drugs against other apicomplexans. In this review, we summarize the recent advances in understanding the Pan and CoA biosynthesis pathways, and the suitability of these pathways as drug targets in Apicomplexa, with a particular focus on the cyst-forming coccidian, Toxoplasma gondii, and the haemosporidian, Plasmodium falciparum. Public Library of Science 2021-12-30 /pmc/articles/PMC8717973/ /pubmed/34969059 http://dx.doi.org/10.1371/journal.ppat.1010124 Text en © 2021 de Vries et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Review de Vries, Laura E. Lunghi, Matteo Krishnan, Aarti Kooij, Taco W. A. Soldati-Favre, Dominique Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets |
title | Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets |
title_full | Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets |
title_fullStr | Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets |
title_full_unstemmed | Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets |
title_short | Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets |
title_sort | pantothenate and coa biosynthesis in apicomplexa and their promise as antiparasitic drug targets |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8717973/ https://www.ncbi.nlm.nih.gov/pubmed/34969059 http://dx.doi.org/10.1371/journal.ppat.1010124 |
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