A redox-sensitive phosphatase regulates glycolysis as a metabolic switch in the bacterial inner membrane.

Abstract

Microorganisms rapidly adjust their metabolism to survive fluctuating environmental conditions, but how they coordinate glycolytic control with redox signals remains unclear. We found that the membrane phosphatase PgpA acts as a redox-sensitive switch to regulate glycolytic flux in <i>Escherichia coli</i>. PgpA dephosphorylates key glycolytic intermediates, glyceraldehyde-3-phosphate and glycerol-3-phosphate, to modulate central metabolism. This activity is controlled by a reversible disulfide bond that forms an inactive dimer under oxidative stress and restores activity when reduced. This redox-dependent regulation enables <i>E. coli</i> to fine-tune metabolism in response to changes in nutrients and oxygen availability. PgpA inactivation increases glucose uptake and promotes metabolism, while constitutive activation impairs growth under anaerobic conditions. We also found that PgpA influences redox homeostasis by regulating glutathione biosynthesis. These findings reveal a negative feedback mechanism in which PgpA integrates glycolysis with redox balance, serving as a central regulator of bacterial metabolic homeostasis in response to environmental changes.