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.
Biological significance: 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.
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