Functional characterization of the first lipoyl-relay pathwayfrom a parasitic protozoan

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dc.citation.titleMolecular Microbiology
dc.citation.volume117
dc.contributor.orcidhttps://orcid.org/0000-0001-7421-2039
dc.contributor.orcidhttps://orcid.org/0000-0001-7164-213X
dc.contributor.orcidhttps://orcid.org/0000-0001-5866-3657
dc.contributor.orcidhttps://orcid.org/0000-0001-5787-5711
dc.contributor.orcidhttps://orcid.org/0000-0002-1444-8661
dc.creatorScattolini, Albertina
dc.creatorLavatelli, Antonela
dc.creatorVacchina, Paola
dc.creatorLambruschi, Daniel Andrés
dc.creatorMansilla, María Cecilia
dc.creatorUttaro, Antonio Domingo
dc.date.accessioned2024-11-08T16:16:35Z
dc.date.available2024-11-08T16:16:35Z
dc.date.issued2022-06
dc.description.abstractLipoic acid (LA) is a sulfur-containing cofactor covalently attached to key enzymes of central metabolism in prokaryotes and eukaryotes. LA can be acquired by scavenging, mediated by a lipoate ligase, or de novo synthesized by a pathway requiring an octanoyltransferase and a lipoate synthase. A more complex pathway, referred to as “lipoyl-relay”, requires two additional proteins, GcvH, the glycine cleavage system H subunit, and an amidotransferase. This route was described so far in Bacillus subtilis and related Gram-positive bacteria, Saccharomyces cerevisiae, Homo sapiens, and Caenorhabditis elegans. Using collections of S. cerevisiae and B. subtilis mutants, defective in LA metabolism, we gathered evidence that allows us to propose for the first time that lipoyl-relay pathways are also present in parasitic protozoa. By a reverse genetic approach, we assigned octanoyltransferase and amidotransferase activity to the products of Tb927.11.9390 (TblipT) and Tb927.8.630 (TblipL) genes of Trypanosoma brucei, respectively. The B. subtilis model allowed us to identify the parasite amidotransferase as the target of lipoate analogs like 8-bromo-octanoic acid, explaining the complete loss of protein lipoylation and growth impairment caused by this compound in T. cruzi. This model could be instrumental for the screening of selective and more efficient chemotherapies against trypanosomiases.
dc.description.filFil: Scattolini, Albertina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Scattolini, Albertina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina.
dc.description.filFil: Lavatelli, Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Lavatelli, Antonela. Centre for Research in Agricultural Genomics. Consejo Superior de Investigaciones Científicas; Spain.
dc.description.filFil: Vacchina, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Lambruschi, Daniel Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Mansilla, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Mansilla, María Cecilia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina.
dc.description.filFil: Uttaro, Antonio Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Uttaro, Antonio Domingo. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina.
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas: P-UE-00392016;
dc.description.sponsorshipFondo para la Investigación Científica y Tecnológica: PICT 2016-1853
dc.description.sponsorshipMinisterio de Ciencia, Tecnología e Innovación Productiva: EULACH 16/T02-0161
dc.description.versionpeerreviewed
dc.format.extent1352–1365
dc.identifier.citationScattolini, Albertina; Lavatelli, Antonela; Vacchina, Paola; Lambruschi, Daniel Andrés; Mansilla, Maria Cecilia; et al.; Functional characterization of the first lipoyl-relay pathway from a parasitic protozoan; Wiley Blackwell Publishing, Inc; Molecular Microbiology; 117; 6; 6-2022; 1352-1365
dc.identifier.issn0950-382X
dc.identifier.urihttps://hdl.handle.net/2133/28070
dc.language.isoen
dc.publisherWiley
dc.relation.publisherversionhttps://doi.org/10.1111/mmi.14913
dc.relation.publisherversionhttps://doi.org/10.1111/mmi.14913 https://onlinelibrary.wiley.com/doi/10.1111/mmi.14913
dc.rightsopenAccess
dc.rights.holderJohn Wiley & Sons Ltd
dc.rights.holderUniversidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas
dc.rights.textAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAmidotransferase
dc.subjectChemotherapy
dc.subjectLipoic acid
dc.subjectTrypanosomatids
dc.titleFunctional characterization of the first lipoyl-relay pathwayfrom a parasitic protozoan
dc.typearticulo
dc.type.versionpublishedVersion

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