Month: September 2022

ADEQUATE BREADTH. “Enrichment for reactions involved in heterotrophic carbon utilization was also observed within pathways for one-carbon (serine pathway) and two-carbon assimilation (Krebs cycle, methylaspartate, and glyoxylate cycle).” https://lnkd.in/dcwZe7b View in LinkedIn

EXPERIMENTAL CORROBORATION. “In addition to a diverse central carbon metabolism, half of the proteinogenic amino acids (G, A, D, N, E, Q, S, T, C, and H) are producible, representing six of the ten amino acids observed in the Miller-Urey experiment.” https://lnkd.in/dcwZe7b View in LinkedIn

KEY REACTIONS. “In this network, building upon a core carbon, energy and nitrogen metabolism, hydrogen sulfide enables the production of sulfur-containing heterogeneous peptides like glutathione, as well as thioester derivatives like S-formyl and S-succinyl glutathione.” https://lnkd.in/dcwZe7b View in LinkedIn

METABOLIC BUILDING BLOCKS. “Intermediates in the degradation and biosynthesis of more complex biomolecules are also observed; 5,6-dihydrouracil is an oxidized catabolic product of uracil and pyrrole is the basic building block for complex heterocyclic aromatic rings like heme” https://lnkd.in/dcwZe7b View in LinkedIn

MINERAL ROOTS. “One fundamental property we focused on is the reliance of these enzymes on iron-sulfur or metal coenzymes, reflecting the notion that modern biochemistry emerged from mineral geochemistry and that metal-based cofactors in modern day enzymes represent a living relic of this contingency.” https://lnkd.in/dcwZe7b View in LinkedIn

QED. “Thus, we report the existence of a phosphate-independent core metabolic network reachable from simple putative prebiotic compounds.” https://lnkd.in/dcwZe7b View in LinkedIn

BRIDGE TO THE PRESENT. “While we cannot rule out possible alternative interpretations of our findings, such as a gradually evolved reliance on metabolic routes that make minimal use of phosphate, it is interesting to ask whether our result could help bridge a fundamental gap between geochemistry and biochemistry.” https://lnkd.in/dcwZe7b View in LinkedIn

PRE-GENETICS. “The properties of the core phosphate-free network suggest that a thioester-based protometabolism may have started from a few, simple geochemically abundant molecules, and expanded to a surprisingly rich and diverse biochemistry, potentially a network-level “fossil” of biosphere metabolism, even prior to the appearance of the phosphate based genetic coding system.” https://lnkd.in/dcwZe7b View in LinkedIn

GENE ORIGINS? “This network could have enabled the synthesis of a diverse set of (bio)chemical compounds, providing precursors for the subsequent rise of informational nucleic acid polymers. Whether and how such a primordial system could have been endowed with features essential for cellular life as we know it, such as collective autocatalysis and information processing, remains an open question.” https://lnkd.in/dcwZe7b View in LinkedIn

SO ENDS this powerful paper which surveyed all known metabolic pathways for clues to early metabolism without phosphate, and thus without genes. Theoretical modeling of this type is an immensely important tool in probing molecular evolution, and will undoubtedly provide hypotheses that are readily tested experimentally. Currently, it is much more difficult to broadly interrogate molecular evolution experimentally, and a narrow series of testable questions is more manageable. View in LinkedIn