title: Mutations in Escherichia coli aceE and ribB genes allow survival of strains defective in the first step of the isoprenoid biosynthesis pathway.
abstract: A functional 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway is required for isoprenoid biosynthesis and hence survival in Escherichia coli and most other bacteria. In the first two steps of the pathway, MEP is produced from the central metabolic intermediates pyruvate and glyceraldehyde 3-phosphate via 1-deoxy-D-xylulose 5-phosphate (DXP) by the activity of the enzymes DXP synthase (DXS) and DXP reductoisomerase (DXR). Because the MEP pathway is absent from humans, it was proposed as a promising new target to develop new antibiotics. However, the lethal phenotype caused by the deletion of DXS or DXR was found to be suppressed with a relatively high efficiency by unidentified mutations. Here we report that several mutations in the unrelated genes aceE and ribB rescue growth of DXS-defective mutants because the encoded enzymes allowed the production of sufficient DXP in vivo. Together, this work unveils the diversity of mechanisms that can evolve in bacteria to circumvent a blockage of the first step of the MEP pathway.
authors.affiliation: Centre for Research in Agricultural Genomics (CRAG) CSIC-IRTA-UAB-UB, Campus UAB Bellaterra, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Perez-Gil
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Uros
authors.forename: Susanna
authors.initials: S
authors.lastname: Sauret-Güeto
authors.forename: L Maria
authors.initials: LM
authors.lastname: Lois
authors.forename: James
authors.initials: J
authors.lastname: Kirby
authors.forename: Minobu
authors.initials: M
authors.lastname: Nishimoto
authors.forename: Edward E K
authors.initials: EE
authors.lastname: Baidoo
authors.forename: Jay D
authors.initials: JD
authors.lastname: Keasling
authors.forename: Albert
authors.initials: A
authors.lastname: Boronat
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodriguez-Concepcion
mesh_terms: D004926:Escherichia coli / Q000166:cytology / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D029968:Escherichia coli Proteins / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000235:genetics*; D019751:Intramolecular Transferases / Q000235:genetics*; D050296:Microbial Viability / Q000235:genetics*; D009154:Mutation; D010428:Pentosephosphates / Q000096:biosynthesis; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics*; D013729:Terpenes / Q000378:metabolism*; D014166:Transferases / Q000172:deficiency
chemical_list: C109460:1-deoxylulose 5-phosphate; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D010428:Pentosephosphates; D011768:Pyruvate Dehydrogenase Complex; D013729:Terpenes; C071147:ribB protein, E coli; D014166:Transferases; C109461:deoxyxylulose-5-phosphate synthase; D019751:Intramolecular Transferases