On the possible origin of protein homochirality, structure, and biochemical function.

Living systems have chiral molecules, e.g., native proteins that almost entirely contain L-amino acids. How protein homochirality emerged from a background of equal numbers of L and D amino acids is among many questions about life's origin. The origin of homochirality and its implications are explored in computer simulations examining the stability and structural and functional properties of an artificial library of compact proteins containing 1:1 (termed demi-chiral), 3:1, and 1:3 ratios of D:L and purely L or D amino acids generated without functional selection. Demi-chiral proteins have shorter secondary structures and fewer internal hydrogen bonds and are less stable than homochiral proteins. Selection for hydrogen bonding yields a preponderance of L or D amino acids. Demi-chiral proteins have native global folds, including similarity to early ribosomal proteins, similar small molecule ligand binding pocket geometries, and many constellations of L-chiral amino acids with a 1.0-Å RMSD to native enzyme active sites. For a representative subset containing 550 active site geometries matching 457 (2) 4-digit (3-digit) enzyme classification (E.C.) numbers, native active site amino acids were generated at random for 472 of 550 cases. This increases to 548 of 550 cases when similar residues are allowed. The most frequently generated sequences correspond to ancient enzymatic functions, e.g., glycolysis, replication, and nucleotide biosynthesis. Surprisingly, even without selection, demi-chiral proteins possess the requisite marginal biochemical function and structure of modern proteins, but were thermodynamically less stable. If demi-chiral proteins were present, they could engage in early metabolism, which created the feedback loop for transcription and cell formation.

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

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.

Formation of Thiophene under Simulated Volcanic Hydrothermal Conditions on Earth-Implications for Early Life on Extraterrestrial Planets?

Thiophene was detected on Mars during the Curiosity mission in 2018. The compound was even suggested as a biomarker due to its possible origin from diagenesis or pyrolysis of biological material. In the laboratory, thiophene can be synthesized at 400 °C by reacting acetylene and hydrogen sulfide on alumina. We here show that thiophene and thiophene derivatives are also formed abiotically from acetylene and transition metal sulfides such as NiS, CoS and FeS under simulated volcanic, hydrothermal conditions on Early Earth. Exactly the same conditions were reported earlier to have yielded a plethora of organic molecules including fatty acids and other components of extant metabolism. It is therefore tempting to suggest that thiophenes from abiotic formation could indicate sites and conditions well-suited for the evolution of metabolism and potentially for the origin-of-life on extraterrestrial planets.

A Possible Primordial Acetyleno/Carboxydotrophic Core Metabolism.

Carbon fixation, in addition to the evolution of metabolism, is a main requirement for the evolution of life. Here, we report a one-pot carbon fixation of acetylene (C2H2) and carbon monoxide (CO) by aqueous nickel sulfide (NiS) under hydrothermal (>100 °C) conditions. A slurry of precipitated NiS converts acetylene and carbon monoxide into a set of C2-4-products that are surprisingly representative for C2-4-segments of all four central CO2-fixation cycles of the domains Bacteria and Archaea, whereby some of the products engage in the same interconversions, as seen in the central CO2-fixation cycles. The results suggest a primordial, chemically predetermined, non-cyclic acetyleno/carboxydotrophic core metabolism. This metabolism is based on aqueous organo-metal chemistry, from which the extant central CO2-fixation cycles based on thioester chemistry would have evolved by piecemeal modifications.

Serpentinization: Connecting Geochemistry, Ancient Metabolism and Industrial Hydrogenation.

Rock⁻water⁻carbon interactions germane to serpentinization in hydrothermal vents have occurred for over 4 billion years, ever since there was liquid water on Earth. Serpentinization converts iron(II) containing minerals and water to magnetite (Fe3O4) plus H2. The hydrogen can generate native metals such as awaruite (Ni3Fe), a common serpentinization product. Awaruite catalyzes the synthesis of methane from H2 and CO2 under hydrothermal conditions. Native iron and nickel catalyze the synthesis of formate, methanol, acetate, and pyruvate-intermediates of the acetyl-CoA pathway, the most ancient pathway of CO2 fixation. Carbon monoxide dehydrogenase (CODH) is central to the pathway and employs Ni° in its catalytic mechanism. CODH has been conserved during 4 billion years of evolution as a relic of the natural CO2-reducing catalyst at the onset of biochemistry. The carbide-containing active site of nitrogenase-the only enzyme on Earth that reduces N2-is probably also a relic, a biological reconstruction of the naturally occurring inorganic catalyst that generated primordial organic nitrogen. Serpentinization generates Fe3O4 and H2, the catalyst and reductant for industrial CO2 hydrogenation and for N2 reduction via the Haber⁻Bosch process. In both industrial processes, an Fe3O4 catalyst is matured via H2-dependent reduction to generate Fe5C2 and Fe2N respectively. Whether serpentinization entails similar catalyst maturation is not known. We suggest that at the onset of life, essential reactions leading to reduced carbon and reduced nitrogen occurred with catalysts that were synthesized during the serpentinization process, connecting the chemistry of life and Earth to industrial chemistry in unexpected ways.