A prebiotic basis for ATP as the universal energy currency.
ATP is universally conserved as the principal energy currency in cells, driving metabolism through phosphorylation and condensation reactions. Such deep conservation suggests that ATP arose at an early stage of biochemical evolution. Yet purine synthesis requires 6 phosphorylation steps linked to AT...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-10-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3001437 |
| _version_ | 1811326298715324416 |
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| author | Silvana Pinna Cäcilia Kunz Aaron Halpern Stuart A Harrison Sean F Jordan John Ward Finn Werner Nick Lane |
| author_facet | Silvana Pinna Cäcilia Kunz Aaron Halpern Stuart A Harrison Sean F Jordan John Ward Finn Werner Nick Lane |
| author_sort | Silvana Pinna |
| collection | DOAJ |
| description | ATP is universally conserved as the principal energy currency in cells, driving metabolism through phosphorylation and condensation reactions. Such deep conservation suggests that ATP arose at an early stage of biochemical evolution. Yet purine synthesis requires 6 phosphorylation steps linked to ATP hydrolysis. This autocatalytic requirement for ATP to synthesize ATP implies the need for an earlier prebiotic ATP equivalent, which could drive protometabolism before purine synthesis. Why this early phosphorylating agent was replaced, and specifically with ATP rather than other nucleoside triphosphates, remains a mystery. Here, we show that the deep conservation of ATP might reflect its prebiotic chemistry in relation to another universally conserved intermediate, acetyl phosphate (AcP), which bridges between thioester and phosphate metabolism by linking acetyl CoA to the substrate-level phosphorylation of ADP. We confirm earlier results showing that AcP can phosphorylate ADP to ATP at nearly 20% yield in water in the presence of Fe3+ ions. We then show that Fe3+ and AcP are surprisingly favoured. A wide range of prebiotically relevant ions and minerals failed to catalyse ADP phosphorylation. From a panel of prebiotic phosphorylating agents, only AcP, and to a lesser extent carbamoyl phosphate, showed any significant phosphorylating potential. Critically, AcP did not phosphorylate any other nucleoside diphosphate. We use these data, reaction kinetics, and molecular dynamic simulations to infer a possible mechanism. Our findings might suggest that the reason ATP is universally conserved across life is that its formation is chemically favoured in aqueous solution under mild prebiotic conditions. |
| first_indexed | 2024-04-13T14:47:31Z |
| format | Article |
| id | doaj.art-f7af47e576c941b8927e0ad0ec9477b9 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-04-13T14:47:31Z |
| publishDate | 2022-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-f7af47e576c941b8927e0ad0ec9477b92022-12-22T02:42:43ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852022-10-012010e300143710.1371/journal.pbio.3001437A prebiotic basis for ATP as the universal energy currency.Silvana PinnaCäcilia KunzAaron HalpernStuart A HarrisonSean F JordanJohn WardFinn WernerNick LaneATP is universally conserved as the principal energy currency in cells, driving metabolism through phosphorylation and condensation reactions. Such deep conservation suggests that ATP arose at an early stage of biochemical evolution. Yet purine synthesis requires 6 phosphorylation steps linked to ATP hydrolysis. This autocatalytic requirement for ATP to synthesize ATP implies the need for an earlier prebiotic ATP equivalent, which could drive protometabolism before purine synthesis. Why this early phosphorylating agent was replaced, and specifically with ATP rather than other nucleoside triphosphates, remains a mystery. Here, we show that the deep conservation of ATP might reflect its prebiotic chemistry in relation to another universally conserved intermediate, acetyl phosphate (AcP), which bridges between thioester and phosphate metabolism by linking acetyl CoA to the substrate-level phosphorylation of ADP. We confirm earlier results showing that AcP can phosphorylate ADP to ATP at nearly 20% yield in water in the presence of Fe3+ ions. We then show that Fe3+ and AcP are surprisingly favoured. A wide range of prebiotically relevant ions and minerals failed to catalyse ADP phosphorylation. From a panel of prebiotic phosphorylating agents, only AcP, and to a lesser extent carbamoyl phosphate, showed any significant phosphorylating potential. Critically, AcP did not phosphorylate any other nucleoside diphosphate. We use these data, reaction kinetics, and molecular dynamic simulations to infer a possible mechanism. Our findings might suggest that the reason ATP is universally conserved across life is that its formation is chemically favoured in aqueous solution under mild prebiotic conditions.https://doi.org/10.1371/journal.pbio.3001437 |
| spellingShingle | Silvana Pinna Cäcilia Kunz Aaron Halpern Stuart A Harrison Sean F Jordan John Ward Finn Werner Nick Lane A prebiotic basis for ATP as the universal energy currency. PLoS Biology |
| title | A prebiotic basis for ATP as the universal energy currency. |
| title_full | A prebiotic basis for ATP as the universal energy currency. |
| title_fullStr | A prebiotic basis for ATP as the universal energy currency. |
| title_full_unstemmed | A prebiotic basis for ATP as the universal energy currency. |
| title_short | A prebiotic basis for ATP as the universal energy currency. |
| title_sort | prebiotic basis for atp as the universal energy currency |
| url | https://doi.org/10.1371/journal.pbio.3001437 |
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