A Nonenzymatic Analog of Pyrimidine Nucleobase Biosynthesis

Abstract

Metabolic theories for the origin of life posit that inorganic catalysts enabled self‐organized chemical precursors to the pathways of metabolism, including those that make genetic molecules. Recently, experiments showing nonenzymatic versions of a number of core metabolic pathways have started to support this idea. However, experimental demonstrations of nonenzymatic reaction sequences along the de novo ribonucleotide biosynthesis pathways are limited. Here we show that all three reactions of pyrimidine nucleobase biosynthesis that convert aspartate to orotate proceed at 60 °C without photochemistry under aqueous conditions in the presence of metals such as Cu2+ and Mn4+. Combining reactions into one‐pot variants is also possible. Life may not have invented pyrimidine nucleobase biosynthesis from scratch, but simply refined existing nonenzymatic reaction channels. This work is a first step towards uniting metabolic theories of life's origin with those centered around genetic molecules.

Positively charged mineral surfaces promoted the accumulation of organic intermediates at the origin of metabolism

“…In this theory, ion concentrations are explicitly expressed as functions of the electric-potential field. The functional form of these expressions is identical to that in Eq (18). The electric-potential field and surface potential are given by…”

“…However, the concentration distributions Ĉi ðrÞ in the cell and membrane are not the same because the electric-potential field ĉðrÞ in these domain are different. Substituting Eq (18) in Eq (12) using Eq (17) furnishes…”

“…We numerically solve this equation using finitedifference methods (see "Numerical Approximation of Steady-State Solutions") subject to the boundary conditions Eqs (14a)-(14b) to compute ĉðrÞ in the cell and membrane for a given set of model parameters. Once the electric-potential field has been computed, it can be backsubstituted in Eq (18) to provide the concentration distributions. S2 Fig represents the results of a case study, showing the radial profiles of the membrane potential, volume-charge density, and ion concentrations that are ascertained by solving Eq (19).…”

“…Hence, the solution strategy that we previously discussed (see "Steayd-State Solutions") for nonreactive species is not applicable here. The concentration distribution of reactive species is also not described by Eq (18). Therefore, we numerically construct the steady-state solutions of Eqs ( 12) and ( 13) for reactive species.…”

“…The metabolism-first hypothesis-one of the main paradigms in prebiotic chemistry-postulates that before the advent of enzymes or genetic codes, geochemical reactions must have emerged spontaneously from simple, inorganic materials and been promoted by naturally occurring catalysts [5][6][7][8][9]. Interestingly, key parts of the core network, including the acetyl-CoA pathway [10,11], tricarboxylic acid cycle [12][13][14], glycolysis and pentose phosphate pathway [15,16], amino-acid and pyrimidine-nucleobase biosynthesis pathways [17,18], and gluconeogenesis [19] have been reproduced non-enzymatically in laboratory experiments. However, whether a collection of these pathways could have spontaneoususly arisen and cooperated in prebiotic cell-like structures to form a self-sustaining protometabolic network is yet to be demonstrated.…”