Issue 48, 2023

A single phosphorylation mechanism in early metabolism – the case of phosphoenolpyruvate

Abstract

Phosphorylation is thought to be one of the fundamental reactions for the emergence of metabolism. Nearly all enzymatic phosphorylation reactions in the anabolic core of microbial metabolism act on carboxylates to give acyl phosphates, with a notable exception – the phosphorylation of pyruvate to phosphoenolpyruvate (PEP), which involves an enolate. We wondered whether an ancestral mechanism for the phosphorylation of pyruvate to PEP could also have involved carboxylate phosphorylation rather than the modern enzymatic form. The phosphorylation of pyruvate with P4O10 as a model phosphorylating agent was found to indeed occur via carboxylate phosphorylation, as verified by mechanistic studies using model substrates, time course experiments, liquid and solid-state NMR spectroscopy, and DFT calculations. The in situ generated acyl phosphate subsequently undergoes an intramolecular phosphoryl transfer to yield PEP. A single phosphorylation mechanism acting on carboxylates appears sufficient to initiate metabolic networks that include PEP, strengthening the case that metabolism emerged from self-organized chemistry.

Graphical abstract: A single phosphorylation mechanism in early metabolism – the case of phosphoenolpyruvate

Supplementary files

Article information

Article type
Edge Article
Submitted
07 aug 2023
Accepted
22 nov 2023
First published
04 dec 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 14100-14108

A single phosphorylation mechanism in early metabolism – the case of phosphoenolpyruvate

J. Zimmermann, R. J. Mayer and J. Moran, Chem. Sci., 2023, 14, 14100 DOI: 10.1039/D3SC04116F

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