Volume 61, Issue 1 e202113625
Research Article
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Concurrent Prebiotic Formation of Nucleoside-Amidophosphates and Nucleoside-Triphosphates Potentiates Transition from Abiotic to Biotic Polymerization

Dr. Huacan Lin

Dr. Huacan Lin

Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037 USA

NSF-NASA Center for Chemical Evolution, Atlanta, GA, 30332 USA

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Dr. Eddy I. Jiménez

Dr. Eddy I. Jiménez

Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037 USA

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Joshua T. Arriola

Joshua T. Arriola

Department of Chemistry and Biochemistry, UC San Diego, 9500 Gilman Drive, La Jolla, CA, 92037 USA

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Prof. Dr. Ulrich F. Müller

Corresponding Author

Prof. Dr. Ulrich F. Müller

Department of Chemistry and Biochemistry, UC San Diego, 9500 Gilman Drive, La Jolla, CA, 92037 USA

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Prof. Dr. Ramanarayanan Krishnamurthy

Corresponding Author

Prof. Dr. Ramanarayanan Krishnamurthy

Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037 USA

NSF-NASA Center for Chemical Evolution, Atlanta, GA, 30332 USA

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First published: 04 November 2021
Citations: 8

In memory of Leslie Orgel

Graphical Abstract

The DAP mediated prebiotic phosphorylation of nucleosides/nucleotides/oligonucleotides produces a spectrum of the corresponding mono-, di-, and tri(amido)phosphorylated derivatives which are substrates for both prebiotic-oligomerization and biotic-polymerization/ligation. The compatibility of the phosphorylation and activation chemistry across a broad spectrum of (oligo)nucleos(t)ide structures suggests a smoother transition from chemistry to biology.

Abstract

Polymerization of nucleic acids in biology utilizes 5′-nucleoside triphosphates (NTPs) as substrates. The prebiotic availability of NTPs has been unresolved and other derivatives of nucleoside-monophosphates (NMPs) have been studied. However, this latter approach necessitates a change in chemistries when transitioning to biology. Herein we show that diamidophosphate (DAP), in a one-pot amidophosphorylation-hydrolysis setting converts NMPs into the corresponding NTPs via 5′-nucleoside amidophosphates (NaPs). The resulting crude mixture of NTPs are accepted by proteinaceous- and ribozyme-polymerases as substrates for nucleic acid polymerization. This phosphorylation also operates at the level of oligonucleotides enabling ribozyme-mediated ligation. This one-pot protocol for simultaneous generation of NaPs and NTPs suggests that the transition from prebiotic-phosphorylation and oligomerization to an enzymatic processive-polymerization can be more continuous than previously anticipated.

Conflict of interest

The authors declare no conflict of interest.

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