Iron catalysis at the origin of life

Camprubí, Eloi; Jordan, Sean; Vasiliadou, Rafaela; Lane, Nick

doi:10.1002/iub.1632

Cited by 127 publications

(118 citation statements)

References 66 publications

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“…At elevated temperature, the F16BP-aldolase substrates G3P and DHAP are unstable and convert within minutes to pyruvate (4). Also at room temperature and under alkaline conditions, they decompose within days (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The network contains many reactive and unstable intermediates, yet its topological organization is widely conserved and considered ancient. It has therefore been extensively debated to what extent this structure could be the result of Darwinian selection and thus be of postgenetic origin or whether the metabolic network topology dates back to a nonenzymatic chemistry (1)(2)(3)(4). A series of recently discovered chemical networks provide evidence for the latter.…”

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confidence: 99%

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Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice

Messner

Driscoll

Piedrafita

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The evolutionary origins of metabolism, in particular the emergence of the sugar phosphates that constitute glycolysis, the pentose phosphate pathway, and the RNA and DNA backbone, are largely unknown. In cells, a major source of glucose and the large sugar phosphates is gluconeogenesis. This ancient anabolic pathway (re-)builds carbon bonds as cleaved in glycolysis in an aldol condensation of the unstable catabolites glyceraldehyde 3-phosphate and dihydroxyacetone phosphate, forming the much more stable fructose 1,6-bisphosphate. We here report the discovery of a nonenzymatic counterpart to this reaction. The in-ice nonenzymatic aldol addition leads to the continuous accumulation of fructose 1,6-bisphosphate in a permanently frozen solution as followed over months. Moreover, the in-ice reaction is accelerated by simple amino acids, in particular glycine and lysine. Revealing that gluconeogenesis may be of nonenzymatic origin, our results shed light on how glucose anabolism could have emerged in early life forms. Furthermore, the amino acid acceleration of a key cellular anabolic reaction may indicate a link between prebiotic chemistry and the nature of the first metabolic enzymes.T he metabolic network is a large cellular system that generates life's building blocks including amino acids, nucleotides, and lipids. Most of the metabolic pathways that participate in this network are well understood, but their evolutionary origin remains an unsolved problem. The network contains many reactive and unstable intermediates, yet its topological organization is widely conserved and considered ancient. It has therefore been extensively debated to what extent this structure could be the result of Darwinian selection and thus be of postgenetic origin or whether the metabolic network topology dates back to a nonenzymatic chemistry (1-4). A series of recently discovered chemical networks provide evidence for the latter. In the presence of simple inorganic ions as found in Archean sediment, and under conditions that are reminiscent of the chemistry that operates in cells, nonenzymatic reactions replicate essential topological elements of the most central metabolic pathways. Nonenzymatic chemical reactions currently replicate glycolysis (including the EmbdenMeyerhof-Parnas pathway, the Entner-Doudoroff pathway, and their many variants), the pentose phosphate pathway, the catabolic reactions of the TCA cycle, and the formation of the methyl group donor S-adenosylmethionine (5-8). Moreover, reactions of glycolysis and the pentose phosphate pathway, as well as reactions replicating the oxidative TCA cycle, can each occur in distinct but unifying reaction milieus, respectively. This implies that simple inorganic catalysts were shaping the topological structure of the metabolic network. In other words, the reactions that sugar phosphates undergo in the presence of the highest concentrated transition metal in Archean sediment [Fe(II)] and the reactions that TCA intermediates undergo in the presence of sulfate radicals are reflected i...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice

Messner

Driscoll

Piedrafita

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…One simple pathway towards a new enzyme functionality could be provided by the recruitment of a catalytic metal ion [142]. However, by no means are all enzymes metalloenzymes.…”

Section: The De Novo Evolution Of New Enzyme Functionsmentioning

confidence: 99%

Conformational dynamics and enzyme evolution

Petrović

Risso

Kamerlin

et al. 2018

J. R. Soc. Interface.

175

184

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Enzymes are dynamic entities, and their dynamic properties are clearly linked to their biological function. It follows that dynamics ought to play an essential role in enzyme evolution. Indeed, a link between conformational diversity and the emergence of new enzyme functionalities has been recognized for many years. However, it is only recently that state-ofthe-art computational and experimental approaches are revealing the crucial molecular details of this link. Specifically, evolutionary trajectories leading to functional optimization for a given host environment or to the emergence of a new function typically involve enriching catalytically competent conformations and/or the freezing out of non-competent conformations of an enzyme. In some cases, these evolutionary changes are achieved through distant mutations that shift the protein ensemble towards productive conformations. Multifunctional intermediates in evolutionary trajectories are probably multi-conformational, i.e. able to switch between different overall conformations, each competent for a given function. Conformational diversity can assist the emergence of a completely new active site through a single mutation by facilitating transition-state binding. We propose that this mechanism may have played a role in the emergence of enzymes at the primordial, progenote stage, where it was plausibly promoted by high environmental temperatures and the possibility of additional phenotypic mutations.

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“…Iron concentrations in the range that, according to current geoscientific knowledge, were dominating the Archean oceans and other aquatic environments 35,36 , have the potential to effectively suppress 1 H-NMR signals of metal-binding metabolites due to paramagnetic line broadening 31 . Metabolites that react on the basis of a metal catalyst, among the most likely precursors of enzymatic reactions 14,37,38 , are likely missed by 1 H-NMR, even when metabolites are at relatively highly concentration. For instance, we show that in the presence of iron, some of the metabolite concentrations used in our previous study as starting conditions, are not detected.…”

Section: H-nmr)mentioning

confidence: 99%

Primordial Krebs-cycle-like non-enzymatic reactions detected by mass spectrometry and nuclear magnetic resonance

et al. 2017

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Metabolism is the process of nutrient uptake and conversion, : Background and executed by the metabolic network. Its evolutionary precursors most likely originated in non-enzymatic chemistry. To be exploitable in a Darwinian process that forms a metabolic pathway, non-enzymatic reactions need to form a chemical network that produces advantage-providing metabolites in a single, life compatible condition. In a hypothesis-generating, large-scale experiment, we recently screened iron and sulfur-rich solutions, and report that upon the formation of sulfate radicals, Krebs cycle intermediates establish metabolism-like non-enzymatic reactivity. A challenge to our results claims that the results obtained by liquid chromatography-selective reaction monitoring (LC-SRM) would not be reproducible by nuclear magnetic resonance spectroscopy ( H-NMR).This study compared the application of the : Methods two techniques to the relevant samples.We detect hundred-to : Results thousand-fold differences in the specific limits of detection between LC-SRM and H-NMR to detect Krebs cycle intermediates. Further, the use of H-NMR was found generally problematic to characterize early metabolic reactions, as Archean-sediment typical iron concentrations cause paramagnetic signal suppression. Consequently, we selected non-enzymatic Krebs cycle reactions that fall within the determined technical limits. We confirm that these proceed unequivocally as evidenced by both LC-SRM and H-NMR.: Conclusions These results strengthen our previous conclusions about the existence of unifying reaction conditions that enables a series of co-occurring metabolism-like non-enzymatic Krebs cycle reactions. We further discuss why constraints applying to metabolism disentangle concentration from importance of any reaction intermediates, and why evolutionary precursors to metabolic pathways must have had much lower metabolite concentrations compared to modern metabolic networks. Research into the chemical origins of life will hence miss out on the chemistry relevant for metabolism if its focus is restricted solely to highly abundant and unreactive metabolites, including when it ignores life-compatibility of the reaction conditions as an essential constraint in enzyme evolution.

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Iron catalysis at the origin of life

Cited by 127 publications

References 66 publications

Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice

Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice

Conformational dynamics and enzyme evolution

Primordial Krebs-cycle-like non-enzymatic reactions detected by mass spectrometry and nuclear magnetic resonance

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