title: Proteome response of Corynebacterium glutamicum to high concentration of industrially relevant C₄ and C₅ dicarboxylic acids.
abstract: More than fifty years of industrial and scientific developments on the amino acid-producer strain Corynebacterium glutamicum has generated an extremely huge knowledge highly applicable to the development of new products. Despite the production of dicarboxylic acids has already been engineered in C. glutamicum, the effect caused by these acids at competitive industrial levels has not yet been described. Thus, aspartic, fumaric, itaconic, malic and succinic acids have been tested on the growth of C. glutamicum to obtain their minimal inhibitory concentrations and their intracellular effects analyzed by 2D-DIGE. This analysis showed the modification of the central metabolism of C. glutamicum, the cross-regulation between malic acid and glucose as well as the aspartic acid utilization as nitrogen source. The analysis of the transcriptional regulators involved in the control of the detected proteins pointed to the ramB gene as a candidate for strain improvement. The analysis of the ΔramB mutant demonstrated its function as an enhancer of the growth speed or resistance level against aspartic, fumaric, itaconic and malic acids in C. glutamicum.
  
  
  CONCLUSIONS
  The effect of dicarboxylic acids addition to the C. glutamicum culture broth has been described. This proteome response is detailed and the deletion of a global regulator (ramB) has been described as a possible improving method for industrial strains. In addition, the consumption of aspartic acid as nitrogen source has been described for the first time in C. glutamicum, as well as, the cross-regulation between malic acid and glucose through the F0F1 respiratory system.
authors.affiliation: Área de Microbiología, Departamento de Biología Molecular, Universidad de León, Campus de Vegazana s/n, 24071 León, Spain.
authors.forename: María F
authors.initials: MF
authors.lastname: Vasco-Cárdenas
authors.forename: Sonia
authors.initials: S
authors.lastname: Baños
authors.forename: Angelina
authors.initials: A
authors.lastname: Ramos
authors.forename: Juan F
authors.initials: JF
authors.lastname: Martín
authors.forename: Carlos
authors.initials: C
authors.lastname: Barreiro
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis*; D048230:Corynebacterium glutamicum / Q000254:growth & development / Q000378:metabolism*; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D020543:Proteome / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D001426:Bacterial Proteins; D003998:Dicarboxylic Acids; D020543:Proteome