Abstract
Phosphoenol pyruvate is the highest-energy phosphate found in living organisms and is one of the most versatile molecules in metabolism. Consequently, it is an essential intermediate in a wide variety of biochemical pathways, including carbon fixation, the shikimate pathway, substrate-level phosphorylation, gluconeogenesis and glycolysis. Triose glycolysis (generation of ATP from glyceraldehyde 3-phosphate via phosphoenol pyruvate) is among the most central and highly conserved pathways in metabolism. Here, we demonstrate the efficient and robust synthesis of phosphoenol pyruvate from prebiotic nucleotide precursors, glycolaldehyde and glyceraldehyde. Furthermore, phosphoenol pyruvate is derived within an α-phosphorylation controlled reaction network that gives access to glyceric acid 2-phosphate, glyceric acid 3-phosphate, phosphoserine and pyruvate. Our results demonstrate that the key components of a core metabolic pathway central to energy transduction and amino acid, sugar, nucleotide and lipid biosyntheses can be reconstituted in high yield under mild, prebiotically plausible conditions.
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Acknowledgements
In memoriam of Harry Lonsdale. This work was supported by the Simons Foundation (31881), the Engineering and Physical Sciences Research Council (EPSRC (EP/K004980/1)), the Leverhulme Trust (RGP-2013-189) and an award from the Origin of Life Challenge.
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The research was conceived by M.W.P. Experiments were conducted by A.J.C. Both authors contributed to the design and analysis of experiments, and to writing the paper.
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Coggins, A., Powner, M. Prebiotic synthesis of phosphoenol pyruvate by α-phosphorylation-controlled triose glycolysis. Nature Chem 9, 310–317 (2017). https://doi.org/10.1038/nchem.2624
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DOI: https://doi.org/10.1038/nchem.2624
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