Pinna, Silvana;
(2022)
Universal energy currencies at the origin of life.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
There is little agreement on how life might have started on Earth. Following life as a guide, phylogenetic and comparative biochemical studies point to an autotrophic origin, with complexity accruing over time. In modern metabolism, the universal energy currency is adenosine triphosphate (ATP), which not only drives metabolism through phosphorylation and condensation reactions but is also key for the synthesis of the informational molecules RNA, DNA, and proteins. Such deep conservation suggests an early origin of ATP, before the emergence of genes or genetically-encoded macromolecular machines such as the ATPase. This thesis explores the plausibility of an early emergence of ATP and the role it might have had at the origin of life. I first confirm earlier work showing moderate (15-20%) ATP yield from the non-enzymatic phosphorylation of ADP by acetyl phosphate (AcP), before systematically exploring the prebiotic context for this synthesis. AcP is a universally conserved intermediate between acetyl-CoA and ATP, bridging between thioester and phosphate metabolism. I show that it is possible to form moderate yields of ATP in a variety of aqueous environments. The combination of AcP and the catalyst Fe³⁺ is surprisingly favoured. No other prebiotically relevant metal ion, mineral, and phosphorylating agent tested here favoured ADP phosphorylation. Nor could AcP phosphorylate other nucleoside diphosphates to the triphosphates. I demonstrate a reaction mechanism that implicates the N7 and the N6 amino group on the adenine ring in the Fe³⁺-catalysed phosphorylation of ADP, implying a deep significance of the adenine base. Finally, I explore how ATP might have facilitated condensation reactions to generate nucleotide and peptide polymers in an aqueous environment, using life as a guide. These efforts met with limited success, confirming that condensation reactions are not facile in water. Nonetheless, my findings overall support the approach of taking life as a guide to study the origin of life.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Universal energy currencies at the origin of life |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| Keywords: | Origin of life, prebiotic chemistry, biochemistry |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10151234 |
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