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Updated: May 31, 2026

Liquid Chromatography Coupled to Refractive Index or Mass Spectrometric Detection for Metabolite Profiling in Lysate-based Cell-free Systems
Published on: September 23, 2021
Progress toward a Nonenzymatic Gluconeogenesis: One-Pot Reactions and Model Systems
Joris Zimmermann1, Quentin Dherbassy1, Noemí Nogal2
1Institut de Science et d'Ingénierie Supramoléculaires (ISIS), CNRS UMR 7006, Université de Strasbourg, 8 Allée Gaspard Monge, 67000 Strasbourg, France.
Abstract:
The earliest cells that can be reconstructed by phylogenetics built their sugars from ketoacids using gluconeogenesis. Metabolic theories for the origin of life suggest that metabolic pathways, including gluconeogenesis, are remnants of a process that started nonenzymatically. However, what conditions might have allowed a nonenzymatic gluconeogenesis to occur remain unclear. Here, we explore the influence of metals and pH on nonenzymatic versions of the reactions of gluconeogenesis. One-pot conditions were developed for the nonenzymatic conversion of phosphoenolpyruvate to 3-phosphoglycerate and for the conversion of fructose-1,6-bisphosphate to glucose-6-phosphate. Proof-of-concept conditions for the conversion of acyl phosphates to thioesters and their subsequent reduction to aldehydes, a reaction sequence seen in the conversion of 1,3-bisphosphoglycerate to glyceraldehyde-3-phosphate, were developed on model compounds. Our findings suggest that an environment capable of initiating a nonenzymatic gluconeogenesis would have needed simultaneous acid and base catalysis, pointing beyond chemistry in bulk solution.
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