A prebiotic precursor to Life’s phosphate transfer system with an ATP analogue and histidyl peptide organocatalysts

06 June 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


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 played an important role in this.


Prebiotic Chemistry
Systems Chemistry
Origins of Life

Supplementary materials

Supporting Information
The Supporting Information contains experimental methods for the hydrolysis reactions, phosphate transfer reactions and the wet-dry physicochemical cycle along with the associated 31P NMR spectra and plots of changes in concentration/yield of phosphorylated species over time. The reaction schemes and rate equations used to determine the rate constants for the hy-drolysis reactions are contained with the fitted plots and a Table of the calculated rate constants. in situ NMR characteri-sation data of the phosphorylated histidyl intermediate are included.


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.