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arxiv: 2510.08410 · v3 · submitted 2025-10-09 · 🧬 q-bio.PE

Intermediate stages in the origin of metabolism at a phosphorylating hydrothermal vent

Natalia Mrnjavac , Nadja K. Hoffmann , Manon L. Schlikker , Maximilian Burmeister , Loraine Schwander , Carolina Garcia Garcia , Max Brabender , Mike Steel
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Daniel H. Huson Sabine Metzger Quentin Dherbassy Bernhard Schink Mirko Basen Joseph Moran Harun Tueysuez Martina Preiner William F. Martin
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Pith reviewed 2026-05-18 09:03 UTC · model grok-4.3

classification 🧬 q-bio.PE
keywords origin of metabolismLUCAhydrothermal ventnative metalsphosphiteprotein structureBacteriaArchaea
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The pith

Enzymatic metabolism in the last universal common ancestor was incomplete and assembled independently in the bacterial and archaeal lineages.

A machine-rendered reading of the paper's core claim, the machinery that carries it, and where it could break.

The paper uses protein structures of metabolic enzymes to map out intermediate stages of their early assembly. It shows that the last universal common ancestor had only a partial metabolic network, with the remaining enzymes added separately after the split into Bacteria and Archaea. Native transition metals served as the original catalysts in place of enzymes, while phosphite supplied energy by driving phosphorylation reactions in water. This combination points to serpentinizing hydrothermal vents as the setting where metabolism could first operate. A sympathetic reader would care because the work supplies a concrete inorganic starting point for how autocatalytic life chemistry could arise without proteins.

Core claim

Enzymatic metabolism in the universal common ancestor was incomplete, undergoing final assembly independently in the lineages leading to Bacteria and Archaea. Native transition metals—Fe0, Co0, Ni0, Pd0—served as the catalytic forerunners of both enzymes and cofactors at metabolic origin while phosphite supplied energy, as it phosphorylates AMP to ADP and serine to phosphoserine using native metal catalysts in water. Phosphite and native metals occur in serpentinizing hydrothermal systems, identifying an energy-supplying, catalytic site of metabolic origin. Cofactors liberated nascent metabolism from native metal catalysts, engendering its autocatalytic state.

What carries the argument

Reconstruction of intermediate states in primordial metabolic assembly through analysis of modern protein structures, which reveals the catalytic precedence of native metals and the energy role of phosphite.

If this is right

  • Many metabolic pathways reached their modern form only after the divergence of Bacteria and Archaea from the last universal common ancestor.
  • Native metals supplied the catalytic activity that enzymes and cofactors later replaced.
  • Phosphite enabled phosphorylation of nucleotides and amino acids in aqueous solution at hydrothermal vents.
  • Cofactors allowed metabolism to become self-sustaining and independent of continuous inorganic inputs.
  • Serpentinizing hydrothermal systems supplied both the catalysts and the energy source needed for the earliest metabolic reactions.

Where Pith is reading between the lines

These are editorial extensions of the paper, not claims the author makes directly.

  • Laboratory simulations of vent fluids with native metals and phosphite could test whether additional reaction steps emerge beyond the ones already shown.
  • The pattern suggests that differences in bacterial and archaeal metabolism reflect separate solutions to completing the same ancestral network.
  • Similar structure-based tracing might be applied to other systems such as replication or membrane synthesis to check for parallel incomplete inheritance from LUCA.
  • Environments on other planets with analogous metal and phosphorus chemistry could be evaluated for comparable early metabolic potential.

Load-bearing premise

Modern protein structures and the phylogenetic distribution of metabolic genes can be used to reconstruct the incomplete metabolic state in the last universal common ancestor and its independent completion after divergence.

What would settle it

Phylogenetic trees or ancestral genome reconstructions showing that all core metabolic enzymes were already present as a complete set in the last universal common ancestor before the bacterial-archaeal split.

Figures

Figures reproduced from arXiv: 2510.08410 by Bernhard Schink, Carolina Garcia Garcia, Daniel H. Huson, Harun Tueysuez, Joseph Moran, Loraine Schwander, Manon L. Schlikker, Martina Preiner, Max Brabender, Maximilian Burmeister, Mike Steel, Mirko Basen, Nadja K. Hoffmann, Natalia Mrnjavac, Quentin Dherbassy, Sabine Metzger, William F. Martin.

Figure 4
Figure 4. Figure 4: Aqueous, phosphite-dependent phosphorylation over metals. A. Oxidation of phosphite (200 mM) to phosphate in water at pH 9, 50°C for 72 h. Each reaction (triplicates) contained 1.5 mmol of Ni (in 1.5 mL) or 0.1 mmol of Pd/C (in 1.0 mL). NH4Cl concentration80, when added, was 75 mM. B. Phosphite in water phosphorylates AMP (100 mM) and serine (100 mM) over Pd in water (Extended Data [PITH_FULL_IMAGE:figure… view at source ↗
Figure 6
Figure 6. Figure 6: B [PITH_FULL_IMAGE:figures/full_fig_p021_6.png] view at source ↗
read the original abstract

The origin of life required the emergence of metabolism, an autocatalytic network of enzymatic reactions that synthesize amino acids, nucleotides and cofactors. At the origin of metabolism there were no enzymes--how did it start? Empirical studies addressing early metabolic evolution are lacking. Harnessing protein structures for metabolic enzymes, we identify intermediate states in primordial metabolic assembly. We show that enzymatic metabolism in the universal common ancestor was incomplete, undergoing final assembly independently in the lineages leading to Bacteria and Archaea. Native transition metals--Fe0, Co0, Ni0, Pd0--served as the catalytic forerunners of both enzymes and cofactors at metabolic origin while phosphite supplied energy, as it phosphorylates AMP to ADP and serine to phosphoserine using native metal catalysts in water. Phosphite and native metals occur in serpentinizing hydrothermal systems, identifying an energy-supplying, catalytic site of metabolic origin. Cofactors liberated nascent metabolism from native metal catalysts, engendering its autocatalytic state.

Editorial analysis

A structured set of objections, weighed in public.

Desk editor's note, referee report, simulated authors' rebuttal, and a circularity audit. Tearing a paper down is the easy half of reading it; the pith above is the substance, this is the friction.

Referee Report

2 major / 1 minor

Summary. The manuscript harnesses protein structures of metabolic enzymes to identify intermediate states in primordial metabolic assembly. It concludes that enzymatic metabolism in the last universal common ancestor (LUCA) was incomplete and underwent final assembly independently in the lineages leading to Bacteria and Archaea. Native transition metals (Fe0, Co0, Ni0, Pd0) are proposed to have served as catalytic forerunners of enzymes and cofactors, with phosphite supplying energy through phosphorylation of AMP to ADP and serine to phosphoserine, as demonstrated in aqueous reactions with these metals. These components are linked to serpentinizing hydrothermal vents as the site of origin.

Significance. If the structural and phylogenetic inferences are robust, the paper offers a coherent scenario for the origin of metabolism that bridges geochemistry and biology, providing a mechanism for the emergence of autocatalytic networks and explaining the divergence of metabolic pathways between domains. The wet-lab validation of phosphite chemistry adds empirical support to the hydrothermal vent hypothesis.

major comments (2)
  1. [protein structure analysis and LUCA inference] The central claim that LUCA metabolism was incomplete with independent completion in Bacteria and Archaea depends on using contemporary protein structures and phylogenetic distributions to reconstruct assembly order. This section does not provide explicit tests to distinguish vertical inheritance from HGT or convergence, which could undermine the evidence for post-LUCA independent assembly if early genes were subject to extensive horizontal transfer.
  2. [phosphorylation experiments] The results showing native metal-catalyzed phosphorylation by phosphite are load-bearing for the energy supply claim at origin. However, the manuscript appears to lack full details on experimental controls, replicate numbers, or quantitative yields in the methods or results sections, making it difficult to assess whether post-hoc choices affect the interpretation.
minor comments (1)
  1. [figures] The figures illustrating the proposed intermediate stages would benefit from explicit indication of which components are supported by structural data versus geochemical inference.

Simulated Author's Rebuttal

2 responses · 0 unresolved

We thank the referee for their thoughtful review and positive evaluation of the significance of our manuscript. We address each of the major comments in detail below and have revised the manuscript accordingly to improve clarity and robustness.

read point-by-point responses

  1. Referee: [protein structure analysis and LUCA inference] The central claim that LUCA metabolism was incomplete with independent completion in Bacteria and Archaea depends on using contemporary protein structures and phylogenetic distributions to reconstruct assembly order. This section does not provide explicit tests to distinguish vertical inheritance from HGT or convergence, which could undermine the evidence for post-LUCA independent assembly if early genes were subject to extensive horizontal transfer.

    Authors: We acknowledge the importance of addressing potential horizontal gene transfer (HGT) and convergence in our phylogenetic inferences. Our analysis uses the distribution of protein structures and sequences across bacterial and archaeal genomes to infer the metabolic repertoire of LUCA, identifying gaps that were filled independently in each domain. To strengthen this, we will add a dedicated subsection discussing the evidence against extensive HGT as the primary driver of the observed patterns. Specifically, core metabolic enzymes show deep phylogenetic conservation consistent with vertical inheritance, and the independent completion of pathways aligns with known domain-specific innovations rather than HGT, which would tend to erase such distinctions. We will also cite supporting studies on the limited impact of HGT on ancient metabolic genes. This revision will make the inference more robust without requiring entirely new analyses. revision: yes

  2. Referee: [phosphorylation experiments] The results showing native metal-catalyzed phosphorylation by phosphite are load-bearing for the energy supply claim at origin. However, the manuscript appears to lack full details on experimental controls, replicate numbers, or quantitative yields in the methods or results sections, making it difficult to assess whether post-hoc choices affect the interpretation.

    Authors: We agree that providing comprehensive experimental details is essential for reproducibility and to address concerns about data interpretation. In the revised version, we will update the Methods section to include: (1) detailed descriptions of all controls, including reactions without phosphite, without metals, and with alternative phosphorus sources; (2) the number of independent replicates (we performed at least three replicates for each condition); and (3) quantitative yields, including HPLC or NMR quantification with standard deviations and statistical significance. We will also clarify the rationale for the conditions chosen and confirm that all relevant data were reported. These additions will allow readers to fully evaluate the results. revision: yes

Circularity Check

0 steps flagged

No significant circularity; derivation rests on independent structural and phylogenetic datasets

full rationale

The paper derives its claims about incomplete LUCA metabolism and post-LUCA independent pathway assembly directly from analysis of modern protein structures and gene presence/absence patterns across domains. These are external empirical inputs, not self-defined or fitted quantities that presuppose the result. Experimental demonstrations of phosphite-driven phosphorylation with native metals are presented as independent geochemical and catalytic evidence. No equations or steps reduce the central inference to its own outputs by construction, and while phylogenetic assumptions about vertical inheritance exist, they do not meet the criteria for load-bearing self-citation or self-definitional circularity. The derivation chain remains self-contained against the cited external benchmarks.

Axiom & Free-Parameter Ledger

0 free parameters · 3 axioms · 0 invented entities

The paper rests on several domain assumptions about ancient geochemistry and phylogeny plus the utility of modern structures for inferring primordial states; no explicit free parameters or newly invented entities are stated in the abstract.

axioms (3)
  • domain assumption Modern protein structures preserve detectable signals of intermediate states in the assembly of primordial metabolic networks.
    Invoked to justify using current enzyme structures to identify LUCA intermediates.
  • domain assumption The last universal common ancestor possessed an incomplete metabolism whose final steps were completed independently after divergence into Bacteria and Archaea lineages.
    Central premise for the claim of independent assembly.
  • domain assumption Serpentinizing hydrothermal systems provide native metals and phosphite at concentrations sufficient for prebiotic phosphorylation.
    Links the lab results to a plausible natural setting.

pith-pipeline@v0.9.0 · 5774 in / 1596 out tokens · 35181 ms · 2026-05-18T09:03:56.394351+00:00 · methodology

discussion (0)

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Reference graph

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