title: A mutant pyruvate dehydrogenase E1 subunit allows survival of Escherichia coli strains defective in 1-deoxy-D-xylulose 5-phosphate synthase.
abstract: The 2-C-methyl-D-erythritol 4-phosphate pathway has been proposed as a promising target to develop new antimicrobial agents. However, spontaneous mutations in Escherichia coli were observed to rescue the otherwise lethal loss of the first two enzymes of the pathway, 1-deoxy-D-xylulose 5-phosphate (DXP) synthase (DXS) and DXP reductoisomerase (DXR), with a relatively high frequency. A mutation in the gene encoding the E1 subunit of the pyruvate dehydrogenase complex was shown to be sufficient to rescue the lack of DXS but not DXR in vivo, suggesting that the mutant enzyme likely allows the synthesis of DXP or an alternative substrate for DXR.
authors.affiliation: Departament de Bioquímica i Biología Molecular, Facultat de Biologia, Universitat de Barcelona. Av. Diagonal 645, 08028 Barcelona, Spain.
authors.forename: Susanna
authors.initials: S
authors.lastname: Sauret-Güeto
authors.forename: Eva María
authors.initials: EM
authors.lastname: Urós
authors.forename: Ester
authors.initials: E
authors.lastname: Ibáñez
authors.forename: Albert
authors.initials: A
authors.lastname: Boronat
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodríguez-Concepción
mesh_terms: D004896:Erythritol / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D009154:Mutation; D010428:Pentosephosphates / Q000096:biosynthesis / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics* / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics* / Q000378:metabolism; D013403:Sugar Phosphates / Q000096:biosynthesis / Q000235:genetics; D014166:Transferases / Q000235:genetics*
chemical_list: C114232:2-C-methylerythritol 4-phosphate; D010428:Pentosephosphates; D021122:Protein Subunits; D011768:Pyruvate Dehydrogenase Complex; D013403:Sugar Phosphates; C453599:pyruvate dehydrogenase multienzyme complex E1; C022219:5-deoxy-D-xylulose 1-phosphate; D014166:Transferases; C109461:deoxyxylulose-5-phosphate synthase; D004896:Erythritol