title: Acetate fluxes in Escherichia coli are determined by the thermodynamic control of the Pta-AckA pathway.
abstract: Escherichia coli excretes acetate upon growth on fermentable sugars, but the regulation of this production remains elusive. Acetate excretion on excess glucose is thought to be an irreversible process. However, dynamic13C-metabolic flux analysis revealed a strong bidirectional exchange of acetate between E. coli and its environment. The Pta-AckA pathway was found to be central for both flux directions, while alternative routes (Acs or PoxB) play virtually no role in glucose consumption. Kinetic modelling of the Pta-AckA pathway predicted that its flux is thermodynamically controlled by the extracellular acetate concentration in vivo. Experimental validations confirmed that acetate production can be reduced and even reversed depending solely on its extracellular concentration. Consistently, the Pta-AckA pathway can rapidly switch from acetate production to consumption. Contrary to current knowledge, E. coli is thus able to co-consume glucose and acetate under glucose excess. These metabolic capabilities were confirmed on other glycolytic substrates which support the growth of E. coli in the gut. These findings highlight the dual role of the Pta-AckA pathway in acetate production and consumption during growth on glycolytic substrates, uncover a novel regulatory mechanism that controls its flux in vivo, and significantly expand the metabolic capabilities of E. coli.
authors.affiliation: LISBP, Université de Toulouse, CNRS, INRA, INSA, Toulouse, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Enjalbert
authors.affiliation: LISBP, Université de Toulouse, CNRS, INRA, INSA, Toulouse, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Millard
authors.affiliation: LISBP, Université de Toulouse, CNRS, INRA, INSA, Toulouse, France.
authors.forename: Mickael
authors.initials: M
authors.lastname: Dinclaux
authors.affiliation: LISBP, Université de Toulouse, CNRS, INRA, INSA, Toulouse, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Portais
authors.affiliation: LISBP, Université de Toulouse, CNRS, INRA, INSA, Toulouse, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Létisse
mesh_terms: D000084:Acetate Kinase / Q000235:genetics / Q000378:metabolism*; D019342:Acetic Acid / Q000378:metabolism*; D002247:Carbon Isotopes; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005285:Fermentation; D015964:Gene Expression Regulation, Bacterial; D005947:Glucose / Q000378:metabolism*; D007553:Isotope Labeling; D007700:Kinetics; D053858:Metabolic Networks and Pathways / Q000235:genetics; D010709:Phosphate Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D002247:Carbon Isotopes; D029968:Escherichia coli Proteins; D010709:Phosphate Acetyltransferase; D000084:Acetate Kinase; D005947:Glucose; D019342:Acetic Acid