Synthesis and breakdown of universal metabolic precursors promoted by iron

Abstract

Life builds its molecules from carbon dioxide (CO₂) and breaks them back down again through the intermediacy of just five metabolites, which are the universal hubs of biochemistry¹. However, it is unclear how core biological metabolism began and why it uses the intermediates, reactions and pathways that it does. Here we describe a purely chemical reaction network promoted by ferrous iron, in which aqueous pyruvate and glyoxylate-two products of abiotic CO₂ reduction^2-4-build up 9 of the 11 intermediates of the biological Krebs (or tricarboxylic acid) cycle, including all 5 universal metabolic precursors. The intermediates simultaneously break down to CO₂ in a life-like regime that resembles biological anabolism and catabolism⁵. Adding hydroxylamine^6-8 and metallic iron into the system produces four biological amino acids in a manner that parallels biosynthesis. The observed network overlaps substantially with the Krebs and glyoxylate cycles^9,10, and may represent a prebiotic precursor to these core metabolic pathways.

Extended Data Figure 1. Transition metal screen.

GC chromatograms showing a reaction network arising from pyruvate and glyoxylate, promoted by transition metal ions at 70 °C (qualitative screen).

Extended Data Figure 2. Calibration lines for carboxylic acids.

Correlation between the concentration of an aqueous solution of carboxylic acids (glyoxylic, glycolic, oxalic, malonic, levulinic, mesaconic and hydroxyketoglutaric + oxopentenedioic) and the measured gas chromatography peak area. Error bars correspond to the standard deviation (three independent runs). 95% confidence bounds computed for 2^nd degree polynomial fits (OriginPro) are shown as orange lines. Calibration lines for glycine, aspartic acid and glutamic acid are shown in Figure S10. Calibration lines for the remaining compounds detected in this study (pyruvate, malate, fumarate, succinate, α-ketoglutarate, isocitrate, cis-aconitate, tricarballylate and alanine) are identical to those we previously reported, for the same analytical setup (Table S1).

Figure 1. Synthesis and breakdown of the universal precursors to biological metabolism promoted by ferrous iron.

a The observed Fe²⁺-promoted reaction network (major pathways are shown using bold reaction arrows). b Time dependence of a reaction network arising from pyruvate and glyoxylate, promoted by Fe²⁺ at 70 °C. Carbon balance refers to the % of carbon atoms observed in solution relative to 0 h and is reported as the average of two independent runs. Product distribution at 24 h is shown in a pie chart. Error bars correspond to the standard deviation. Values for hydroxyketoglutarate also include oxopentanedioate.

Figure 2. A comparison of the observed reaction network with the TCA cycle (left) and the glyoxylate cycle (right).

Overlapping intermediates and reactions are shown in black. Those not observed in the synthetic reaction cycle are in grey.