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.

Pyrophosphate and Irreversibility in Evolution, or why PPi Is Not an Energy Currency and why Nature Chose Triphosphates

“…To see whether PP i might have had a role in primordial energetics, the reactions of the core ( Wimmer et al, 2021 ) that involve PP i or ATP were identified and polarized in the biosynthetic direction, that is, from H 2 and CO 2 toward cell mass synthesis. In Lipman’s view, PP i was an environmental energy source, a substrate that assumes a thermodynamic role as an educt residing on the left side of an enzymatic reaction, while in Kornberg’s view PP i is synthesized in metabolism via ATP hydrolysis and assumes a kinetic role as a product that is removed from the right side of the reaction.…”

“…Note that these calculations entail only biosynthetic costs and do not consider energy spilling ( Tempest and Neijssel, 1984 ) or maintenance energy, which can exceed biosynthesis by a factor of 3 in exponential growth ( Russell and Cook, 1995 ; Russell, 2007 ), and by more under energy limitation ( Lever et al, 2015 ). b The proportion of PP i forming steps in monomer biosynthesis was calculated as the total cost for the monomer multiplied by the fraction of PP i forming steps among ATP hydrolyzing steps en route to nucleoside monophosphates ( Wimmer et al, 2021 ). c The proportion of PP i forming steps in polymerization takes the costs of proofreading, assembly and modification from Lever et al (2015) into account.…”

“…The 36 metabolic reactions involving inorganic pyrophosphate (PP i ; Supplementary Table S1 ) in the biosynthetic core were taken from supplemental data of Wimmer et al (2021) . Reaction R00720 involving IMP synthesis was removed from the core because it is not essential.…”

“…Though this line of reasoning (comparative physiology) can be questioned, it is the same reasoning that underlies the view that PP i is an ancient energy currency. The conserved core of metabolism is a set of roughly 400 reactions that generates the 20 canonical amino acids, the four bases of RNA and DNA, and the cofactors required for their synthesis from H 2 , CO 2 , NH 3 , H 2 S, P i , and inorganic salts ( Wimmer et al, 2021 ). Because of its universally conserved nature, this biosynthetic core of chemical reactions (though not necessarily all of it enzymes) was present in the last universal common ancestor, LUCA, and has persisted in all lineages throughout evolution over the last 4 billion years since their divergence from LUCA ( Weiss et al, 2016 ).…”

To What Inanimate Matter Are We Most Closely Related and Does the Origin of Life Harbor Meaning?

“…It of course depends on who one asks and where one thinks how life might have arisen. If life arose from the reaction of H 2 and CO 2 in hydrothermal vents [103,125], as we contend, then its structure emerges from the geometry of carbon bonds as carbon oxides undergo reduction with electrons and hydrides from H 2 , reacting to generate longer and more diverse carbon chains [9] while reacting with other elements like nitrogen and sulfur to produce the amino acids, nucleosides, and cofactors that comprise life [127,128], through overall reactions that are thermodynamically favored [129] under the conditions of hydrothermal vents.…”