Synthetic non-oxidative glycolysis enables complete carbon conservation

A non-oxidative, cyclic pathway—termed non-oxidative glycolysis—is designed and constructed that enables complete carbon conservation in sugar catabolism to acetyl-coenzyme A, and can be used to achieve a 100% carbon yield to fuels and chemicals. Much of the pyruvate produced from sugars by glycolysis, a metabolic pathway found in almost all living organisms, is decarboxylated to produce acetyl-coenzyme A (CoA) for various biosynthetic purposes. Along the way, however, pyruvate decarboxylation loses a carbon equivalent, limiting the theoretical carbon yield to only two moles of two-carbon (C2) metabolites per mole of hexose. James Liao and colleagues have constructed a non-oxidative, cyclic pathway that allows the production of stoichiometric amounts of C2 metabolites from hexose, pentose and triose phosphates without carbon loss. This pathway, termed non-oxidative glycolysis (NOG), enables complete carbon conservation in sugar catabolism to acetyl-CoA The authors demonstrate NOG both in vitro and in engineered Escherichia coli strains. Industrially this new approach could be used to produce bio-alcohols, fatty acids, biodiesel and isoprenoids from sugars. Glycolysis, or its variations, is a fundamental metabolic pathway in life that functions in almost all organisms to decompose external or intracellular sugars. The pathway involves the partial oxidation and splitting of sugars to pyruvate, which in turn is decarboxylated to produce acetyl-coenzyme A (CoA) for various biosynthetic purposes. The decarboxylation of pyruvate loses a carbon equivalent, and limits the theoretical carbon yield to only two moles of two-carbon (C2) metabolites per mole of hexose. This native route is a major source of carbon loss in biorefining and microbial carbon metabolism. Here we design and construct a non-oxidative, cyclic pathway that allows the production of stoichiometric amounts of C2 metabolites from hexose, pentose and triose phosphates without carbon loss. We tested this pathway, termed non-oxidative glycolysis (NOG), in vitro and in vivo in Escherichia coli. NOG enables complete carbon conservation in sugar catabolism to acetyl-CoA, and can be used in conjunction with CO2 fixation1 and other one-carbon (C1) assimilation pathways2 to achieve a 100% carbon yield to desirable fuels and chemicals.