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Metabolic characterization of Escherichia coli regulator CreC in bioreactor assays. The great importance of metabolic control by gene regulation in microorganisms is evidenced by the wide and complex net of transcription regulators that hierarchically interact to manage a highly controlled expression of genes codifying for different catabolic and anabolic enzymes. Most global regulators in E. coli which work in this manner are well characterized (ArcA, Fnr, FadR, etc). Nevertheless, some of them are poorly known, such as CreBC, a two-component system involved in the regulation of carbohydrates catabolism. Previous studies in our laboratory found that mutants having the constitutive allele creC510, and a deletion of arcA, had a particular phenotipe with high levels of reduced equivalents and increased oxygen uptake. To further investigate the role of CreC on carbon metabolism independently of ArcA, we first compared the metabolic profiles of the wild type strain K1060, with K1060C (creC510), and DC1060 (creC), in shaken flasks cultures. These experiments strongly suggested that CreC has an important role in carbon metabolism, that was reflected by the significative differences observed in the production of the main fermentative acids (lactate, formate and acetate) when the wild type was compared to the creC strain. To go deeper in these metabolic studies, we performed metabolic assays in a 3 Lts bioreactor, where the growing conditions are strictly controlled, allowing higher biomass and fermentative acids yields. Cells were grown in M9, a mineral medium, supplemented with glucose or glycerol. Aeration conditions were also manipulated to generate low oxygen availability. Basic biomass parameters were measured, including cell dry weight (CDW), growth curves and max in the four different growth conditions obtained combining each carbon source with high and low aeration. There was a small but significant increase in max in the creC deletion mutant (DC1060), compared to the wt strain, when grown in glucose, but no differences were observed for this parameter when glycerol was used as the carbon source. More interesting results were observed in the organic acids profiles. For glucose, lactate secretion diminished from 67±9 mM in K1060 to 9±2 mM in DC1060, i.e. decreased 87%. By contrast, in the mutant strain formate and acetate augmented 195% (from 11,0±1,4 mM to 32,5±2,8mM) and 68% (from 13,1±2,1 to 22,1± 1,2) respectively. For glycerol, the main products were formate and acetate. As for glucose, both acids were increased, but in this case just 30% (from 8±2mM to 10±1 for formate and from 7,3±0,0mM to 6±1mM for acetate). Succinate production was really low in both carbon sources, specially in glycerol. However, it was significantly higher for the deletion mutant in glucose, where it reached a 3,5 fold increase. These results correspond to those obtained in shaken flasks, confirming the importance of the global regulator CreC in the genetic regulation of the central metabolism of E. coli, which was more evident in the cultures grown in biorreactors.