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Synthetic non-oxidative glycolysis enables complete carbon conservation

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Abstract

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.

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Figure 1: Structure of oxidative (EMP) and non-oxidative glycolysis (NOG).
Figure 2: Three FBP-dependent NOG networks.
Figure 3: In vitro NOG.
Figure 4: In vivo conversion of xylose to acetate using NOG.

Change history

  • 30 September 2013

    Panel labels b and c were assigned to the wrong panels in Fig. 4 and have been corrected.

  • 30 October 2013

    Author affiliations and a text citation to Fig. 1a have been corrected, and a minor change to Fig. 1 has been made.

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Acknowledgements

This work was partially supported by National Science Foundation (NSF) grant MCB-1139318 and Department of Energy (DOE) grant DE0-SC0006698. I.W.B. was supported by NSF Integrative Graduate Education and Research Traineeship (IGERT) grant no. 0903720.

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Authors

Contributions

I.W.B. and J.C.L. conceived the project, designed the experiments, analysed the data, and wrote the manuscript. I.W.B. performed experiments, and T.-S.L. assisted in experiments.

Corresponding author

Correspondence to James C. Liao.

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The authors declare no competing financial interests.

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This file contains Supplementary Figures 1-8, Supplementary Tables 1-8 and additional references. (PDF 1153 kb)

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Bogorad, I., Lin, TS. & Liao, J. Synthetic non-oxidative glycolysis enables complete carbon conservation. Nature 502, 693–697 (2013). https://doi.org/10.1038/nature12575

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