Autocatalytic chemical networks at the origin of metabolism

Joana C. Xavier, Wim Hordijk, Stuart Kauffman, Mike Steel, William F. Martin

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)


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 H2 and CO2 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.

Original languageEnglish
Article number20192377
JournalProceedings of the Royal Society B: Biological Sciences
Issue number1922
Publication statusPublished - 11 Mar 2020


  • Acetogens
  • Autocatalytic networks
  • Biochemical evolution
  • Methanogens
  • Origin of life
  • Origin of metabolism


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