Synthesis and breakdown of universal metabolic precursors promoted by iron

• Published in: Nature (London) 2019-05, Vol.569 (7754), p.104-107
• Main Authors: Muchowska, Kamila B., Varma, Sreejith J., Moran, Joseph
• Format: Article
• Language: English
• Subjects: 140/131; 639/638/45/321/1155; 639/638/904; Amino acids; Analysis; Biochemistry; Biosynthesis; Carbon dioxide; Carbon Dioxide - metabolism; Cell metabolism; Chemical reactions; Chemical Sciences; Chemical synthesis; Chemistry; Citric Acid Cycle; Ferrous Compounds - metabolism; Glyoxylates - metabolism; Humanities and Social Sciences; Hydroxylamine - metabolism; Influence; Intermediates; Iron; Iron (Nutrient); Iron - metabolism; Letter; Metabolic Networks and Pathways; Metabolic pathways; Metabolism; Metabolites; Metabolomics; multidisciplinary; NMR; Nuclear magnetic resonance; Organic chemistry; Other; Phosphorus; Prebiotics; Precursors; Pyruvic acid; Pyruvic Acid - metabolism; Science; Tricarboxylic acid cycle
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-019-1151-1

Life builds its molecules from carbon dioxide (CO 2 ) and breaks them back down again through the intermediacy of just five metabolites, which are the universal hubs of biochemistry 1 . 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 CO 2 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 CO 2 in a life-like regime that resembles biological anabolism and catabolism 5 . 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. A chemical reaction network that overlaps with the biological Krebs and glyoxylate cycles arises from pyruvate and glyoxylate in the presence of iron, suggesting how early metabolic pathways might have arisen from CO 2 .