The origin of intermediary metabolism

TLDR

The citric acid cycle is central to intermediary metabolism in autotrophs, and in certain chemoautotrophs its reductive form drives synthesis by incorporating CO₂ into cycle intermediates. The study aims to explore emergent reaction networks by filtering the Beilstein database with physical and chemical constraints relevant to a CO₂‑based model system. The authors analyze a CO₂‑based C,H,O model system powered by redox couples, filtering the Beilstein database with physical and chemical constraints to identify viable reaction networks. Analysis of 3.5 million Beilstein entries yielded 153 molecules encompassing all 11 reductive citric acid cycle members, and a few selection rules further constrain this set, indicating the model’s relevance to biogenesis and suggesting that the universal pathway’s metabolism may uniquely arise from organic chemistry.

Abstract

The core of intermediary metabolism in autotrophs is the citric acid cycle. In a certain group of chemoautotrophs, the reductive citric acid cycle is an engine of synthesis, taking in CO(2) and synthesizing the molecules of the cycle. We have examined the chemistry of a model system of C, H, and O that starts with carbon dioxide and reductants and uses redox couples as the energy source. To inquire into the reaction networks that might emerge, we start with the largest available database of organic molecules, Beilstein on-line, and prune by a set of physical and chemical constraints applicable to the model system. From the 3.5 million entries in Beilstein we emerge with 153 molecules that contain all 11 members of the reductive citric acid cycle. A small number of selection rules generates a very constrained subset, suggesting that this is the type of reaction model that will prove useful in the study of biogenesis. The model indicates that the metabolism shown in the universal chart of pathways may be central to the origin of life, is emergent from organic chemistry, and may be unique.