The metabolic networks of microorganisms are remarkably robust to genetic and environmental perturbations. This robustness stems from redundancies such as gene duplications, isoenzymes, alternative metabolic pathways, and also from non-enzymatic reactions. In the oxidative branch of the pentose-phosphate pathway (oxPPP), 6-phosphogluconolactone hydrolysis into 6-phosphogluconate is catalysed by 6-phosphogluconolactonase (Pgl) but in the absence of the latter, the oxPPP flux is thought to be maintained by spontaneous hydrolysis. However, in ΔpglEscherichia coli, an extracellular pathway can also contribute to pentose-phosphate synthesis. This raises question as to whether the non-enzymatic reaction can compensate for the absence of 6-phosphogluconolactonase and, ultimately, on the role of 6-phosphogluconolactonase in central metabolism. Our results indicate that in the absence of Pgl, this bypass pathway accounts for the entire flux into the oxPPP, suggesting that non-enzymatic hydrolysis does not compensate for the absence of Pgl and demonstrating that Pgl is critical for an efficiently functioning oxPPP.

Phosphogluconolactonase as the linchpin of an efficient pentose phosphate pathway