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On the aqueous origins of the condensation polymers of life

Nature Reviews Chemistry volume 8, pages 817–832 (2024)Cite this article

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Abstract

Water is essential for life as we know it, but it has paradoxically been considered inimical to the emergence of life. Proteins and nucleic acids have sustained evolution and life for billions of years, but both are condensation polymers, suggesting that their formation requires the elimination of water. This presents intrinsic challenges at the origins of life, including how condensation polymer synthesis can overcome the thermodynamic pressure of hydrolysis in water and how nucleophiles can kinetically outcompete water to yield condensation products. The answers to these questions lie in balancing thermodynamic activation and kinetic stability. For peptides, an effective strategy is to directly harness the energy trapped in prebiotic molecules, such as nitriles, and avoid the formation of fully hydrolysed monomers. In this Review, we discuss how chemical energy can be built into precursors, retained, and released selectively for polymer synthesis. Looking to the future, the outstanding goals include how nucleic acids can be synthesized, avoiding the formation of fully hydrolysed monomers and what caused information to flow from nucleic acids to proteins.

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Fig. 1: Prebiotic monomer syntheses exploit the intrinsic energy of prebiotic nitriles.
Fig. 2: Biochemical strategies for condensation polymer growth and their spontaneous fragmentation.
Fig. 3: Challenges in the synthesis of α-peptides from α-amino acids.
Fig. 4: Formation of α-peptides from α-aminonitriles without the α-amino acid intermediaries.
Fig. 5: Spontaneous differentiation of the Strecker pathway to α-peptides and the non-proteinogenic peptide bonds in coenzyme A by the intrinsic reactivity of prebiotic nitriles.
Fig. 6: Nucleic acid-templated polymerization of nucleic acids.
Fig. 7: Electrophilic activation of nucleoside-5′-phosphates.
Fig. 8: Aqueous phosphorylation of nucleosides.
Fig. 9: Selective phosphorylation reactions.

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Acknowledgements

M.W.P. discloses support for the research of this work from Engineering and Physical Sciences Research Council (EPSRC) grant EP/X011755/1 and Simons Foundation grant 1154101. D.W. discloses support for the research of this work from Royal Society fellowship URF\R1\231450.

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    Daniel Whitaker & Matthew W. Powner

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Whitaker, D., Powner, M.W. On the aqueous origins of the condensation polymers of life. Nat Rev Chem 8, 817–832 (2024). https://doi.org/10.1038/s41570-024-00648-5

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