Metal-Pyridoxal Cooperativity in Nonenzymatic Transamination

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(24), P. 13357 - 13370

Published: June 6, 2023

Coenzymes are involved in ≥30% of enzymatic reactions and likely predate enzymes, going back to prebiotic chemistry. However, they considered poor organocatalysts, thus their pre-enzymatic function remains unclear. Since metal ions known catalyze metabolic the absence here we explore influence on coenzyme catalysis under conditions relevant origin life (20–75 °C, pH 5–7.5). Specifically, Fe or Al, two most abundant metals Earth's crust, were found exhibit substantial cooperative effects transamination catalyzed by pyridoxal (PL), a scaffold used roughly 4% all enzymes. At 75 °C 7.5 mol % loading PL/metal ion, Fe3+-PL was be 90-fold faster at catalyzing than PL alone 174-fold Fe3+ alone, whereas Al3+-PL 85-fold 38-fold Al3+ alone. Under milder conditions, >1000 times those Pyridoxal phosphate (PLP) exhibited similar behavior PL. Experimental theoretical mechanistic studies indicate that rate-determining step PL-metal-catalyzed is different from metal-free biological PL-based catalysis. Metal coordination lowers pKa PL-metal complex several units slows hydrolysis imine intermediates up 259-fold. Coenzymes, specifically derivatives, could have useful catalytic even before

Language: Английский

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The protometabolic nature of prebiotic chemistry

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(21), P. 7359 - 7388

Published: Jan. 1, 2023

This tutorial review revises the main synthetic pathways of prebiotic chemistry, suggesting how they could be wired through common intermediates and catalytic cycles, as well boundary conditions under which would become protometabolic.

Language: Английский

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A prebiotic Krebs cycle analog generates amino acids with H2 and NH3 over nickel

Chem, Journal Year: 2024, Volume and Issue: 10(5), P. 1528 - 1540

Published: Feb. 27, 2024

Hydrogen (H2) has powered microbial metabolism for roughly 4 billion years. The recent discovery that it also fuels geochemical analogs of the most ancient biological carbon fixation pathway sheds light on origin metabolism. However, remains unclear whether H2 can sustain more complex nonenzymatic reaction networks. Here, we show drives reductive amination six ketoacids and glyoxylate to give corresponding amino acids in good yields using ammonium concentrations ranging from 6 150 mM. Catalytic amounts nickel or ground meteorites enable these reactions at 22°C pH 8. same conditions promote an H2-dependent ketoacid-forming aldol chemistry co-occurs with amination, producing a continuous network resembling acid synthesis metabolic core microbes. results support hypothesis earliest biochemical networks could have emerged without enzymes RNA.

Language: Английский

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Hydrogen Drives Part of the Reverse Krebs Cycle under Metal or Meteorite Catalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(51)

Published: Oct. 17, 2022

Hydrogen (H2 ) is a geological source of reducing electrons that thought to have powered the metabolism last universal common ancestor all extant life, and still metabolized by various modern organisms. It has been suggested H2 drove geochemical analogue some or reverse Krebs cycle at emergence metabolic network, catalyzed metals, but this yet be demonstrated experimentally. Herein, we show three consecutive steps cycle, converting oxaloacetate into succinate, can driven without enzymes in one-pot as agent under mild conditions compatible with biological chemistry. Low catalytic amounts nickel (10-20 mol %) platinum group metals (0.1-1 even small ground meteorites were found promote reductive chemistry temperatures between 5 60 °C over wide pH range, including 7. These results lend additional support hypothesis geologically produced hydrogen metal catalysts could initiated early networks.

Language: Английский

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Quantifying Catalysis at the Origin of Life**

Chemistry - A European Journal, Journal Year: 2023, Volume and Issue: 29(53)

Published: Aug. 14, 2023

Abstract The construction of hypothetical environments to produce organic molecules such as metabolic intermediates or amino acids is the subject ongoing research into emergence life. Experiments specifically focused on an anabolic approach typically rely a mineral catalyst facilitate supply organics that may have produced prebiotic building blocks for Alternatively true catalytic system, could be sacrificially oxidized in production organics, necessitating emergent ‘life’ turn virgin materials each iteration processes. aim this perspective view current ‘metabolism‐first’ literature through lens chemistry evaluate need higher activity and analyses. While many elegant studies detailed chemical under geologically plausible biologically relevant conditions, few appear do so with sub‐stoichiometric amounts metals minerals. Moving toward rigorous analyses necessary demonstrate viability elusive cornerstone hypotheses: catalysis. We emphasize future work should decreased loading, increased productivity, and/or evidence

Language: Английский

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Prebiotic Synthesis of Aspartate Using Life’s Metabolism as a Guide

Life, Journal Year: 2023, Volume and Issue: 13(5), P. 1177 - 1177

Published: May 12, 2023

A protometabolic approach to the origins of life assumes that conserved biochemistry metabolism has direct continuity with prebiotic chemistry. One most important amino acids in modern biology is aspartic acid, serving as a nodal metabolite for synthesis many other essential biomolecules. Aspartate’s complicated by instability its precursor, oxaloacetate. In this paper, we show use biologically relevant cofactor pyridoxamine, supported metal ion catalysis, sufficiently fast offset oxaloacetate’s degradation. Cu2+-catalysed transamination oxaloacetate pyridoxamine achieves around 5% yield within 1 h, and can operate across broad range pH, temperature, pressure. addition, downstream product β-alanine may also take place same reaction system at very low yields, directly mimicking an archaeal route. Amino group transfer pyridoxal shown from aspartate alanine, but reverse (alanine aspartate) shows poor yield. Overall, our results related indeed be synthesised via pathways foreshadow presence simple ions.

Language: Английский

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Metal ions turn on a stereoselective nonenzymatic reduction of keto acids by the coenzyme NADH

Chem, Journal Year: 2024, Volume and Issue: 10(8), P. 2564 - 2576

Published: June 13, 2024

The relationship between genetic molecules and metabolism is one of the longest-standing problems for origin life. A central molecule within early coenzyme nicotinamide adenine dinucleotide (NAD(H)), a modified ribonucleotide reducing agent. Yet, without enzymes, NADH does not reduce carbonyl compounds, its primary metabolic substrates, leading to an apparent paradox regarding role in evolution metabolism. We now report that abundant metal ions turn on nonenzymatic, stereoselective, potentially primordial reduction reaction keto acids by NADH. Kinetic, mechanistic, computational studies elucidate mechanism way stereochemistry transferred. Complexes metals with RNA-derived coenzymes could have mediated transition from inorganic organic agents propagation chirality

Language: Английский

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Aqueous microdroplets promote C–C bond formation and sequences in the reverse tricarboxylic acid cycle

Nature Ecology & Evolution, Journal Year: 2023, Volume and Issue: 7(11), P. 1892 - 1902

Published: Sept. 7, 2023

Language: Английский

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Redox-Controlled Shunts in a Synthetic Chemical Reaction Cycle

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(17), P. 9672 - 9678

Published: April 24, 2023

Shunts, alternative pathways in chemical reaction networks (CRNs), are ubiquitous nature, enabling adaptability to external and internal stimuli. We introduce a CRN which the recovery of Michael-accepting species is driven by oxidation chemistry. Using weak oxidants can enable access two shunts within this with different kinetics reduced number side reactions compared main cycle that strong oxidants. Furthermore, we strategy recycle one products under flow conditions partially reverse control product speciation throughout time. These findings new levels over artificial CRNs, redox chemistry, narrowing gap between synthetic natural systems.

Language: Английский

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Pinpointing Conditions for a Metabolic Origin of Life: Underlying Mechanisms and the Role of Coenzymes

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(20), P. 3032 - 3043

Published: Oct. 5, 2024

ConspectusFamously found written on the blackboard of physicist Richard Feynman after his death was phrase, "What I cannot create, do not understand." From this perspective, recreating origin life in lab is a necessary condition for achieving deep theoretical understanding biology. The "metabolism-first" hypothesis one leading frameworks life. A complex self-organized reaction network thought to have been driven into existence as chemical path least resistance release free energy environment that could otherwise be dissipated, rerouting from planetary processes organic chemistry. To increase complexity, network, initially under catalysis provided by its geochemical environment, must produced catalysts pruned existing flux through or expanded it new directions. This boot-strapping process would gradually lessen dependence initial catalytic and allow persist using own making. Eventually, leads seemingly inseparable interdependence at heart biology between (coenzymes, enzymes, genes) metabolic pathways synthesize them. Experimentally, primary challenge recreate conditions where such emerged. However, near infinite number microenvironments sources available early Earth elsewhere poses an enormous combinatorial challenge. constrain search, our has surveying reactions making up core some most ancient chemolithoautotrophic metabolisms, which consist only small repeating mechanisms, occur nonenzymatically. give fresh viewpoint first part account, we organized results search (along with important other laboratories) mechanism, rather than pathway. We expect identifying common set each type mechanism will help pinpoint emergence resembling metabolism. Many mechanisms were wide variety nonenzymatic conditions. Others, carboxylate phosphorylation C-C bond formation CO

Language: Английский

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