The origin of intermediary metabolism

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 CO2 and synthesizing the molecules of the cycle. We have examined the chemistry of a model system of C, H, and O tha t starts with carbon dioxide and reductants and uses redox couples as the e nergy source. To inquire into the reaction networks that might emerge, we s tart with the largest available database of organic molecules, Beilstein on -line, and prune by a set of physical and chemical constraints applicable t o the model system. From the 3.5 million entries in Beilstein we emerge wit h 153 molecules that contain all 11 members of the reductive citric acid cy cle. 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 i n the universal chart of pathways may be central to the origin of life, is emergent from organic chemistry, and may be unique.