Rewriting Pathways to Life for Carbon Conservation

Production of chemicals and fuels using biological method is a desirable goal that has been pursued for decades, if not centuries. Although success stories have been increasing recently, biological processes are still difficult to compete with traditional chemical processes.  One of the major limitations of biological processes lies in the central pathways that support all life processes on earth.  In particular, glycolysis, a fundamental metabolic pathway in life that exists in almost all organisms to decompose sugars, proceeds in a way that loses 1/3 of the carbon to CO2 when producing most of the fuels and chemicals.  As a result, almost all biofuel and biochemical production processes suffer a significant loss in yield. The pathway proceeds through 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.  In this talk, we will discuss the design and construction of 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, and can be used in conjunction with CO2 fixation and other one-carbon (C1) assimilation pathways to achieve 100% carbon yield to desirable fuels and chemicals.