Revisiting the coupling of fatty acid to phospholipid synthesis in bacteria with FapR regulation

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dc.citation.titleMolecular Microbiology
dc.citation.volume114
dc.contributor.orcidhttps://orcid.org/0000-0003-4380-9152
dc.creatorMachinandiarena, Federico
dc.creatorNakamatsu, Leandro
dc.creatorSchujman, Gustavo Enrique
dc.creatorDe Mendoza, Diego
dc.creatorAlbanesi, Daniela
dc.date.accessioned2024-11-06T14:41:22Z
dc.date.available2024-11-06T14:41:22Z
dc.date.issued2020-07-16
dc.description.abstractA key aspect in membrane biogenesis is the coordination of fatty acid to phospholipid synthesis rates. In most bacteria, PlsX is the first enzyme of the phosphatidic acid synthesis pathway, the common precursor of all phospholipids. Previously, we proposed that PlsX is a key regulatory point that synchronizes the fatty acid synthase II with phospholipid synthesis in Bacillus subtilis. However, understanding the basis of such coordination mechanism remained a challenge in Gram-positive bacteria. Here, we show that the inhibition of fatty acid and phospholipid synthesis caused by PlsX depletion leads to the accumulation of long-chain acyl-ACPs, the end products of the fatty acid synthase II. Hydrolysis of the acyl-ACP pool by heterologous expression of a cytosolic thioesterase relieves the inhibition of fatty acid synthesis, indicating that acyl-ACPs are feedback inhibitors of this metabolic route. Unexpectedly, inactivation of PlsX triggers a large increase of malonyl-CoA leading to induction of the fap regulon. This finding discards the hypothesis, proposed for B. subtilis and extended to other Gram-positive bacteria, that acyl-ACPs are feedback inhibitors of the acetyl-CoA carboxylase. Finally, we propose that the continuous production of malonyl-CoA during phospholipid synthesis inhibition provides an additional mechanism for fine-tuning the coupling between phospholipid and fatty acid production in bacteria with FapR regulation.
dc.description.filFil: Machinandiarena, Federico. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET). Departamento de Microbiología; Argentina.
dc.description.filFil: Nakamatsu, Leandro. División de Biología Sintética, Ingeniería Metabólica S.A. (INMET); Argentina.
dc.description.filFil: Schujman, Gustavo Enrique. División de Biología Sintética, Ingeniería Metabólica S.A. (INMET); Argentina.
dc.description.filFil: Schujman, Gustavo Enrique. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET). Departamento de Microbiología; Argentina.
dc.description.filFil: De Mendoza, Diego. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET). Departamento de Microbiología; Argentina.
dc.description.filFil: Albanesi, Daniela. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET). Departamento de Microbiología; Argentina.
dc.description.sponsorshipAgencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación (Agencia I+D+i): PICT 2016-1594, PICT 2014-2474
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
dc.description.versionpeerreviewed
dc.format.extent1-11
dc.identifier.e-issn1365-2958
dc.identifier.issn0950-382X
dc.identifier.urihttps://hdl.handle.net/2133/28056
dc.language.isoen
dc.publisherWiley
dc.relation.publisherversionhttps://doi.org/10.1111/mmi.14574
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/doi/10.1111/mmi.14574
dc.rightsopenAccess
dc.rights.holderMachinandiarena, Federico
dc.rights.holderNakamatsu, Leandro
dc.rights.holderSchujman, Gustavo Enrique
dc.rights.holderDe Mendoza, Diego
dc.rights.holderAlbanesi, Daniela
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.subjectAcetyl-CoA carboxylase
dc.subjectAcyl-ACP
dc.subjectFatty acid kinase
dc.subjectGram-positive bacteria
dc.subjectMembranebiogenesis regulation
dc.subjectPlsX
dc.subjectPhospholipids
dc.titleRevisiting the coupling of fatty acid to phospholipid synthesis in bacteria with FapR regulation
dc.typearticulo
dc.type.versionpublishedVersion

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