Origin & Evolution of Life

A Prebiotic Precursor To Life’s Phosphate Transfer System With An ATP Analogue And Histidyl Peptide Organocatalysts

By Keith Cowing
Status Report
June 23, 2023
Filed under
A Prebiotic Precursor To Life’s Phosphate Transfer System With An ATP Analogue And Histidyl Peptide Organocatalysts
Histidyls catalyse the hydrolysis of imidazole phosphate. a) Reaction overview and conditions. b) The histidyl amino acid and peptide residues used to study the hydrolysis reaction. c) A representative 31P NMR spectra over time for the reaction of 50 mM imidazole phosphate (Ca2+ salt) and 50 mM of histidine catalyst in 0.5 M MOPS buffer and 0.1 M citric acid at pH 7.5 and 22 °C. d) The changes in concentration of imidazole phosphate (solid lines) and the hydrolysis product orthophosphate (dashed lines) over time. The reactions were repeated in duplicate or triplicate – data points are the mean value and error bars are the standard deviation. ImP = imidazole phosphate, Pi = orthophosphate. — chemrxiv.org

Biochemistry is dependent upon enzyme catalysts accelerating key reactions. At the origin of life, prebiotic chemistry must have incorporated catalytic reactions.

Whilst this would have yielded much needed amplification of certain reaction products, it would come at the possible cost of rapidly depleting the high energy molecules that acted as chemical fuels. Here, we demonstrate a prebiotic phosphate transfer system involving a kinetically stable and thermodynamically activated ATP analogue (imidazole phosphate) and histidyl peptides which function as organocatalytic enzyme analogues.

We demonstrate that histidyl peptides catalyse phosphorylations via a phosphorylated histidyl intermediate. We integrate these histidyl catalysed phosphorylations into a complete prebiotic scenario whereby inorganic phosphate is incorporated into organic compounds though physicochemical wet-dry cycles.

Our work demonstrates a plausible system for the catalysed production of phosphorylated compounds on the early Earth and how organocatalytic peptides, as enzyme precursors, could have an important role in this.

Oliver R. Maguire Author, Iris B. A. Smokers, Bob G. Oosterom, Alla Zheliezniak, Wilhelm T. S. Huck



Explorers Club Fellow, ex-NASA Space Station Payload manager/space biologist, Away Teams, Journalist, Lapsed climber, Synaesthete, Na’Vi-Jedi-Freman-Buddhist-mix, ASL, Devon Island and Everest Base Camp veteran, (he/him) 🖖🏻