Phosphorylation, oligomerization and self-assembly in water under potential prebiotic conditions

Abstract

Prebiotic phosphorylation of (pre)biological substrates under aqueous conditions is a critical step in the origins of life. Previous investigations have had limited success and/or require unique environments that are incompatible with subsequent generation of the corresponding oligomers or higher-order structures. Here, we demonstrate that diamidophosphate (DAP)—a plausible prebiotic agent produced from trimetaphosphate—efficiently (amido)phosphorylates a wide variety of (pre)biological building blocks (nucleosides/tides, amino acids and lipid precursors) under aqueous (solution/paste) conditions, without the need for a condensing agent. Significantly, higher-order structures (oligonucleotides, peptides and liposomes) are formed under the same phosphorylation reaction conditions. This plausible prebiotic phosphorylation process under similar reaction conditions could enable the systems chemistry of the three classes of (pre)biologically relevant molecules and their oligomers, in a single-pot aqueous environment.

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Figure 1: DAP-mediated phosphorylation of nucleosides/tides demonstrating the potential to generate and progress through the successive levels of nucleotides and oligonucleotides under similar conditions.
Figure 2: DAP-induced phosphorylation and esterification of glycerol with short-chain fatty acids give rise to simple mimics of phospholipids, leading to formation of protocell-like structures under the same reaction conditions, signifying the single-pot transition of simple building blocks to higher-order self-assemblies.
Figure 3: DAP phosphorylates amino acids in water while activating them towards the formation of oligopeptides in the same reaction setting.

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Acknowledgements

The work was supported by a grant from the Simons Foundation to R.K. (327124) and NASA (NNX14AP59G). This is manuscript #29523 from The Scripps Research Institute. The authors thank M. Wood, T. Fassel and W.B. Kiosses of the Core Microscope Facility of TSRI, M. Janssen for initial TEM measurements, J. Kelly's laboratory for DLS measurements, L. Leman for help with analysis of peptides and the S.F. Dowdy laboratory for MALDI-TOF analysis. The authors also thank R. Ghadiri, D. Deamer, S. Mansy, P. Banerjee, J. Szostak, G. Joyce and our lab members for discussions.

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R.K. conceived the project. R.K., C.G., S.B., M.K. and E.-K.K. designed the experiments. C.G. and S.B. performed the nucleoside/nucleotide/oligonucleotide phosphorylation experiments. M.K., S.B. and C.G. performed the amino acid phosphorylation experiments. M.K. performed the liposome studies. E.-K.K. and S.B. made the initial observations of DAP-mediated phosphorylation. R.K. wrote the paper with input from C.G., S.B., M.K. and E.-K.K. All authors discussed the results and commented on the manuscript. C.G., S.B. and M.K. contributed equally to this work.

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Correspondence to Ramanarayanan Krishnamurthy.

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The authors declare no competing financial interests.

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Gibard, C., Bhowmik, S., Karki, M. et al. Phosphorylation, oligomerization and self-assembly in water under potential prebiotic conditions. Nature Chem 10, 212–217 (2018). https://doi.org/10.1038/nchem.2878

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