Membrane synthesis in Escherichia coli is coordinated with growth via post-translational regulation

Abstract Every growing cell must produce enough membrane to contain itself. However, the mechanisms by which cells couple the rate of membrane synthesis with the rate of growth remain unresolved. By measuring precursors, intermediates, and enzymes of the fatty acid and phospholipid synthesis pathways of Escherichia coli during steady-state growth, we find that while transcriptional regulation maintains membrane synthesis capacity at a stable level, the actual rate of phospholipid synthesis is mediated by allosteric control of a single enzyme (PlsB). PlsB activity also strongly influences flux into the synthesis pathway of lipopolysaccharide, the second-most abundant membrane component in Gram negative bacteria. Furthermore, we find that membrane synthesis rates are highly sensitive to changes in fatty acid precursor concentrations, enabling rapid responses to environmental perturbations. Such responses are modulated by the global regulator ppGpp, which we hypothesize acts as an emergency brake on PlsB activity to prevent imbalances between membrane synthesis and synthesis of lipoproteins that tether the outer membrane to the cell. The combination of dynamic post-translational regulation with maintenance of stable synthesis capacity ensures both robustness and responsiveness of bacterial membrane synthesis during growth.