Glucose-1,6-Bisphosphate, a Key Metabolic Regulator, Is Synthesized by a Distinct Family of α-Phosphohexomutases Widely Distributed in Prokaryotes
Niels Neumann, Simon Friz, Karl Forchhammer
Abstract
Glc-1,6-BP is known as an essential activator of phosphoglucomutase (PGM) and other members of the αPHM superfamily, making it a central regulator in glycogen metabolism, glycolysis, amino sugar formation as well as bacterial cell wall and capsule formation. Despite this essential role in carbon metabolism, its origin in prokaryotes has so far remained elusive. In this study we identify a member of a specific αPHM subfamily as the first bacterial Glc-1,6-BP synthase, forming free Glc-1,6-BP by using Frc-1,6-BP as phosphoryl-donor. PGMs of this subfamily are widely distributed among prokaryotes including human commensals and pathogens. By showing that a distinct subfamily member can also form Glc-1,6-BP, we provide evidence that Glc-1,6-BP synthase activity is a general feature of this group.