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THE ALGORITHM. “The algorithm adds metabolites and reactions to an initial seed set, iteratively asking whether any new reaction could take place given the available substrates, until convergence to a final set of reactions and metabolites (or “scope”).” https://lnkd.in/dcwZe7b View in LinkedIn

STARTING BLOCKS. “To this end we adopted the network expansion algorithm, which simulates the emergence of metabolic networks from a predefined set of compounds.” https://lnkd.in/dcwZe7b View in LinkedIn

SEARCH PARAMETERS. “We started by searching for regions of global metabolism that could be accessible starting from simple molecules likely to have been geochemically abundant on early Earth.” https://lnkd.in/dcwZe7b View in LinkedIn

OVERCOMING BOTTLENECKS. “Statistical analysis of the physiochemical properties of enzymes within this network show an enrichment for iron-sulfur and transition metal coenzymes. By broadening our analysis of protometabolism with the inclusion of different types of coenzyme precursor couplings, we further show that thioesters, rather than phosphate, could have enabled this core metabolism to overcome energetic bottlenecks, supporting the feasibility of a metabolically rich thioester-based early biochemistry.” https://lnkd.in/dcwZe7b View in LinkedIn

CRYPTIC METABOLIC FOSSIL. “The major finding we report below is the discovery of a phosphate-independent core metabolism hidden within this biosphere-level network. This core protometabolism is capable of supporting the synthesis of a broad set of biomolecules, including several amino acids and carboxylic acids.” https://lnkd.in/dcwZe7b View in LinkedIn

ENZYME SURROGATES. “In exploring the prebiotic relevance of metabolic reactions that in extant life are catalyzed by highly evolved, efficient, and specific protein-based enzymes, we implicitly formulate the hypothesis that many of such reactions could have been initially catalyzed to a much weaker and less specific extent by a number of small molecules.” https://lnkd.in/dcwZe7b View in LinkedIn

METABOLIC UNIVERSE. “Given that our goal is to shed light on processes that predate the estimated last universal common ancestor (LUCA), and given the long-term reshuffling of genes among organisms through horizontal-gene transfer, we focused our analysis on a global, biosphere-level biochemical network, which encompasses all known metabolic reactions across all organisms.” https://lnkd.in/dcwZe7b View in LinkedIn

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

WHERE MATH FAILS. “Classical GR governs the evolution of black holes for a long time, but at some exponentially large time it must break down. The breakdown, and what comes after it, is not well understood.” (GR = General Relativity). https://lnkd.in/d3Fw6gf View in LinkedIn

AMPLITUDE. “Further analysis showed significant enrichment for metabolites/reactions involved in various carbon fixation pathways, including the dicarboxylate-hydroxybutyrate cycle, the hydroxypropionate bi-cycle, and the reductive TCA cycle, which has been previously proposed as a primitive carbon fixation pathway in ancient autotrophs.” https://lnkd.in/dcwZe7b View in LinkedIn