The Autotrophic Core: An Ancient Network of 404 Reactions Converts H2, CO2, and NH3 into Amino Acids, Bases, and Cofactors

Abstract

The metabolism of cells contains evidence reflecting the process by which they arose. Here, we have identified the ancient core of autotrophic metabolism encompassing 404 reactions that comprise the reaction network from H₂, CO₂, and ammonia (NH₃) to amino acids, nucleic acid monomers, and the 19 cofactors required for their synthesis. Water is the most common reactant in the autotrophic core, indicating that the core arose in an aqueous environment. Seventy-seven core reactions involve the hydrolysis of high-energy phosphate bonds, furthermore suggesting the presence of a non-enzymatic and highly exergonic chemical reaction capable of continuously synthesizing activated phosphate bonds. CO₂ is the most common carbon-containing compound in the core. An abundance of NADH and NADPH-dependent redox reactions in the autotrophic core, the central role of CO₂, and the circumstance that the core's main products are far more reduced than CO₂ indicate that the core arose in a highly reducing environment. The chemical reactions of the autotrophic core suggest that it arose from H₂, inorganic carbon, and NH₃ in an aqueous environment marked by highly reducing and continuously far from equilibrium conditions. Such conditions are very similar to those found in serpentinizing hydrothermal systems.

Keywords: chemolithoautotrophy; early metabolism; hydrothermal vents; origins of life; serpentinizing systems.

Figure 1

(a) A general map of core metabolism. The arrows in the map do not cover every atom in every cofactor, amino acid, or base, showing main mass contributions instead. A dot indicates that radical S-adenosyl methionine (SAM) enzymes are involved in the biosynthetic pathway leading to the product. [S] indicates that sulfur is incorporated in the biosynthetic pathway. (b) Cofactors indicated by a star are required in the pathway from H₂ and CO₂ to pyruvate in either acetogens or methanogens or both. (c) The composition of cells in terms of its main components and elemental contributions to dry weight (from [31]).

Figure 2

The autotrophic core network of 404 reactions underlying Figure 1. The undirected bipartite graph comprises 404 reaction nodes (displayed as gray diamonds) and 380 compound nodes (circles). The 46 target compounds are colored blue; other compounds involved in the reactions appear orange. Target compounds correspond to the core compounds in Figure 1. Each compound participating in a reaction is connected to the respective reaction node with an edge. Compounds are sized according to node degree (number of reactions the compound takes place in). For example, H₂O appears either as reactant or product in 125 reactions and is the most frequent compound in the 404 reactions (see also Table 1). In primordial metabolic processes, before the existence of enzymes, a more limited spectrum of compounds than those in Figure 1 was provided by the environment. Compound nodes are labeled if they are targets or if the node degree is ≥20. Note that FeS clusters are not included in this figure since their synthesis cannot be reconstructed using KEGG. The network contains only l-amino acids.