Role of the FhlA transcriptional activator in metabolic changes in Escherichia coli during fermentation of mixed carbon sources at acidic pH

Escherichia coli formate hydrogen lyase (FHL) complexes are involved in the acid resistance mechanisms during fermentation, neutralizing intracellular formate to molecular hydrogen (H₂). The current study elucidates the role of the FhlA transcriptional activator and formate metabolism in metabolic regulation during the fermentation of glucose, glycerol and formate at pH 5.5. It was shown that FhlA has a role in bacterial growth properties. The extracellular formate concentration was higher by ∼10 mM (at 20 h) and ∼8 mM (at 72 h) in cells lacking FhlA. Moreover, bacterial cells regulate ΔpH and maintain viability by the formate-lactate exchange during glycerol utilization. The formate to ethanol pathway is suggested for the regulation of pH_in. It can be concluded that fermenting cells efficiently regulate metabolic pathways to adapt and maintain viability under acidic conditions.