Modern cells embody metabolic networks containing thousands of elements and form autocatalytic sets of molecules that produce copies of themselves. How the first self-sustaining metabolic networks arose at life's origin is a major open question. Autocatalytic sets smaller than metabolic networks were proposed as transitory intermediates at the origin of life, but evidence for their role in prebiotic evolution is lacking. Here, we identify reflexively autocatalytic food-generated networks (RAFs)—self-sustaining networks that collectively catalyse all their reactions—embedded within microbial metabolism. RAFs in the metabolism of ancient anaerobic autotrophs that live from H ₂ and CO ₂ provided with small-molecule catalysts generate acetyl-CoA as well as amino acids and bases, the monomeric components of protein and RNA, but amino acids and bases without organic catalysts do not generate metabolic RAFs. This suggests that RAFs identify attributes of biochemical origins conserved in metabolic networks. RAFs are consistent with an autotrophic origin of metabolism and furthermore indicate that autocatalytic chemical networks preceded proteins and RNA in evolution. RAFs uncover intermediate stages in the emergence of metabolic networks, narrowing the gaps between early Earth chemistry and life.

Research on the origin of life is highly heterogeneous. After a peculiar historical development, it still includes strongly opposed views which potentially hinder progress. In the 1st Interdisciplinary Origin of Life Meeting, early-career researchers gathered to explore the commonalities between theories and approaches, critical divergence points, and expectations for the future. We find that even though classical approaches and theories—e.g., bottom-up and top-down, RNA world vs. metabolism-first—have been prevalent in origin of life research, they are ceasing to be mutually exclusive and they can and should feed integrating approaches. Here we focus on pressing questions and recent developments that bridge the classical disciplines and approaches, and highlight expectations for future endeavours in origin of life research.

Rock–water–carbon interactions germane to serpentinization in hydrothermal vents have occurred for over 4 billion years, ever since there was liquid water on Earth. Serpentinization converts iron(II) containing minerals and water to magnetite (Fe₃O₄) plus H₂. The hydrogen can generate native metals such as awaruite (Ni₃Fe), a common serpentinization product. Awaruite catalyzes the synthesis of methane from H₂ and CO₂ under hydrothermal conditions. Native iron and nickel catalyze the synthesis of formate, methanol, acetate, and pyruvate—intermediates of the acetyl-CoA pathway, the most ancient pathway of CO₂ fixation. Carbon monoxide dehydrogenase (CODH) is central to the pathway and employs Ni⁰ in its catalytic mechanism. CODH has been conserved during 4 billion years of evolution as a relic of the natural CO₂-reducing catalyst at the onset of biochemistry. The carbide-containing active site of nitrogenase—the only enzyme on Earth that reduces N₂—is probably also a relic, a biological reconstruction of the naturally occurring inorganic catalyst that generated primordial organic nitrogen. Serpentinization generates Fe₃O₄ and H₂, the catalyst and reductant for industrial CO₂ hydrogenation and for N₂ reduction via the Haber–Bosch process. In both industrial processes, an Fe₃O₄ catalyst is matured via H₂-dependent reduction to generate Fe₅C₂ and Fe₂N respectively. Whether serpentinization entails similar catalyst maturation is not known. We suggest that at the onset of life, essential reactions leading to reduced carbon and reduced nitrogen occurred with catalysts that were synthesized during the serpentinization process, connecting the chemistry of life and Earth to industrial chemistry in unexpected ways.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Self-sustaining autocatalytic networks play a central role in living systems, from metabolism at the origin of life, simple RNA networks and the modern cell, to ecology and cognition. A collectively autocatalytic network that can be sustained from an ambient food set is also referred to more formally as a ‘reflexively autocatalytic food-generated’ (RAF) set. In this paper, we first investigate a simplified setting for studying RAFs, which is nevertheless relevant to real biochemistry and which allows an exact mathematical analysis based on graph-theoretic concepts. This, in turn, allows for the development of efficient (polynomial-time) algorithms for questions that are computationally intractable (NP-hard) in the general RAF setting. We then show how this simplified setting for RAF systems leads naturally to a more general notion of RAFs that are ‘generative’ (they can be built up from simpler RAFs) and for which efficient algorithms carry over to this more general setting. Finally, we show how classical RAF theory can be extended to deal with ensembles of catalysts as well as the assignment of rates to reactions according to which catalysts (or combinations of catalysts) are available.