All extant life forms depend, directly or indirectly, on the autotrophic fixation of the dominant elements of the biosphere: carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur. We have earlier presented the canonical network of reactions that constitute the anabolism of a reductive chemoautotroph. Separating this network into subgraphs reveals several empirical generalizations: (1) acetate (acetyl-CoA), pyruvate, phosphoenol pyruvate, oxaloacetate, and 2-oxoglutarate serve as universal starting points for all pathways leading to the universal building blocks-20 amino acids and 4 ribonucleotide triphosphates; (2) all pathways are anabolic; (3) all reactions operate by complete utilization of outputs with no molecules left behind as waste, ensuring conservation of information; (4) the core metabolome of 120 compounds is acidic, consisting of compounds containing phosphoric or carboxylic acid or both; and (5) the core network is both brittle-vulnerable to a single break-and robust-having persisted for 4 billion years. Preliminary analysis of the chemical reactions and resultant structures reveals (a) a sparseness among possible molecular structures; (b) subdomains in the network; and (c) restriction of anabolism to a small set of rudimentary organic reactions with limited diversity in chemical mechanisms. These generalizations have implications for biogenesis and trophic ecology.

The assumption that all biological catalysts are either proteins or ribozymes leads to an outstanding enigma of biogenesis-how to determine the synthetic pathways to the monomers for the efficient formation of catalytic macromolecules in the absence of any such macromolecules. The last 60 years have witnessed chemists developing an understanding of organocatalysis and ligand field theory, both of which give demonstrable low-molecular-weight catalysts. We assume that transition-metal-ligand complexes are likely to have occurred in the deep ocean trenches by the combination of naturally occurring oceanic metals and ligands synthesized from the emergent CO(2), H(2), NH(3), H(2)S, and H(3)PO(4). We are now in a position to investigate experimentally the metal-ligand complexes, their catalytic function, and the reaction networks that could have played a role in the development of metabolism and life itself.

Chemoautorophs that fix carbon by the reductive tricarboxylic acid cycle represent one of the dominant bacterial life forms that make a major contribution to biomass production. From the viewpoint of biogenesis, construction of a canonical chart of intermediary metabolism for this class of organisms may help us to understand early cellular evolution and point us to the last universal common ancestor. Data-mining the KEGG Pathways database enabled us to integrate required biosynthetic pathways and derive a chart that represents the complete anabolic network of a reductive chemoautotroph. Compounds of this metabolic network together constitute a representative minimal metabolome that comprises 287 metabolites. These compounds have been classified into different groups including those compounds that form nodes in the network. It can be seen that a relatively sparse set of organic chemical reactions dominate the anabolic synthesis in the assembly of the minimal autotrophic metabolome. Empirical generalizations that result from analyzing this metabolic network may aid in elucidating selection rules that govern its emergence and further evolution and may also help in delineating attributes that impart the observed robustness to these metabolites.