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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.

SUBMITTER: Muchowska KB

PROVIDER: S-EPMC6517266 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Glucosinolates, a group of sulfur-rich thioglucosides found in plants of the order Brassicales, have attracted a lot of interest as chemical defenses of plants and health promoting substances in human diet. They are accumulated separately from their hydrolyzing enzymes, myrosinases, within the intact plant, but undergo myrosinase-catalyzed hydrolysis upon tissue disruption. This results in various biologically active products, e.g. isothiocyanates, simple nitriles, epithionitriles, and organic thiocyanates. While formation of isothiocyanates proceeds by a spontaneous rearrangement of the glucosinolate aglucone, aglucone conversion to the other products involves specifier proteins under physiological conditions. Specifier proteins appear to act with high specificity, but their exact roles and the structural bases of their specificity are presently unknown. Previous research identified the motif EXXXDXXXH as potential iron binding site required for activity, but crystal structures of recombinant specifier proteins lacked the iron cofactor. Here, we provide experimental evidence for the presence of iron (most likely Fe2+) in purified recombinant thiocyanate-forming protein from Thlaspi arvense (TaTFP) using a Ferene S-based photometric assay as well as Inductively Coupled Plasma-Mass Spectrometry. Iron binding and activity depend on E266, D270, and H274 suggesting a direct interaction of Fe2+ with these residues. Furthermore, we demonstrate presence of iron in epithiospecifier protein and nitrile-specifier protein 3 from Arabidopsis thaliana (AtESP and AtNSP3). We also present a homology model of AtNSP3. In agreement with this model, iron binding and activity of AtNSP3 depend on E386, D390, and H394. The homology model further suggests that the active site of AtNSP3 imposes fewer restrictions to the glucosinolate aglucone conformation than that of TaTFP and AtESP due to its larger size. This may explain why AtNSP3 does not support epithionitrile or thiocyanate formation, which likely requires exact positioning of the aglucone thiolate relative to the side chain.

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Synthesis and breakdown of universal metabolic precursors promoted by iron.

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