Autocatalytic chemical networks at the origin of metabolism

Abstract

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.

The structure of autocatalytic networks, with application to early biochemistry

“…Application. In [36], the metabolism of two ancient prokaryotic species was explored for the presence of maxRAFs. Here, we use the network of one of those species, Methanococcus maripaludis, to explore the differences between the maxRAF, maxCAF and max-pRAF.…”

“…Here, we use the network of one of those species, Methanococcus maripaludis, to explore the differences between the maxRAF, maxCAF and max-pRAF. The food set is FS2 detailed in Table S1 of [36], including inorganic molecules, inorganic catalysts and abiotic organic carbon -with the addition of nicotinamide adenine dinucleotide (NAD) as the sole organic catalyst (44 molecule types in total). We chose NAD as it was the organic catalyst with the highest impact on the maxRAF size.…”

“…We chose NAD as it was the organic catalyst with the highest impact on the maxRAF size. The network is the same as reported for M. maripaludis in [36] with 965 reactions including pooling reactions (operational reactions that equate synonymous cofactors). The sizes for maxRAF, maxCAF and max-pRAF reported next (produced by the software CatlyNet [12]) also include pooling reactions.…”

“…With this new food set, which tests the network in an abiotic setting where NAD was generated by the environment, we obtain a maxCAF with 12 reactions using 20 food molecules, a maxRAF with 84 reactions using 34 food molecules, and a max-pRAF with 540 reactions using 38 food molecules. Note the large maxRAF expansion that NAD alone allows for (one order of magnitude), as with the same food set without NAD, the maxRAF for M. maripaludis consisted of eight reactions only (see Table S1 in [36]). It is also important to notice that the max-pRAF is far from the size of the full network.…”

“…Nevertheless, comparing the metabolism of organisms across the tree (or network) of life provides some clues into the nature of early metabolism. In particular, the metabolic networks of bacteria and archaea share certain structural features, and mathematical and computational techniques have recently helped identify these [36].…”