How Droplets Can Accelerate Reactions─Coacervate Protocells as Catalytic Microcompartments

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(14), P. 1885 - 1895

Published: July 5, 2024

ConspectusCoacervates are droplets formed by liquid–liquid phase separation (LLPS) and often used as model protocells–primitive cell-like compartments that could have aided the emergence of life. Their continued presence membraneless organelles in modern cells gives further credit to their relevance. The local physicochemical environment inside coacervates is distinctly different from surrounding dilute solution offers an interesting microenvironment for prebiotic reactions. Coacervates can selectively take up reactants enhance effective concentration, stabilize products, destabilize lower transition states, therefore play a similar role micellar catalysts providing rate enhancement selectivity reaction outcome. Rate must been essential origins life enabling chemical reactions occur at appreciable rates overcoming competition hydrolysis.In this Accounts, we dissect mechanisms which coacervate protocells accelerate provide selectivity. These similarly be exploited control cellular processes. First, affect concentration copartitioning or exclusion product inhibitor. Second, change energy landscape taking place droplets. more apolar than rich charged moieties, stability reactants, states products. crowded nature favor complexation large molecules such ribozymes. locally proton water activity facilitate involving (de)protonation step, condensation sensitive hydrolysis. Not only core, but also surface provides site with gradients pH, charge. catalytic amino acids localize like divalent metal ions, leading Lastly, these properties certain pathways, thereby give over outcome.These illustrated case study on ribozyme coacervates, there fine balance between reactivity tuned composition. Furthermore, both catalyze selectivity, demonstrating functioned enzyme-like microcompartments

Language: Английский

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Active droplets through enzyme-free, dynamic phosphorylation

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 17, 2024

Abstract Life continuously transduces energy to perform critical functions using stored in reactive molecules like ATP or NADH. dynamically phosphorylates active sites on proteins and thereby regulates their function. Inspired by such machinery, regulating supramolecular has gained traction. Enzyme-free, synthetic systems that use dynamic phosphorylation regulate processes have not yet been reported, our knowledge. Here, we show an enzyme-free reaction cycle consumes the phosphorylating agent monoamidophosphate transiently histidine histidine-containing peptides. The phosphorylated species are labile deactivate through hydrolysis. exhibits versatility tunability, allowing for of multiple precursors with a tunable half-life. Notably, resulting products can peptide’s phase separation, leading droplets require continuous conversion fuel sustain. will be valuable as model biological but also offer insights into protocell formation.

Language: Английский

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Characterization of the Phosphotransferase from Bacillus subtilis 1101 That Is Responsible for the Biotransformation of Zearalenone

Toxins, Journal Year: 2025, Volume and Issue: 17(1), P. 21 - 21

Published: Jan. 3, 2025

Bacillus microorganisms play an important role in the zearalenone (ZEA) biotransformation process natural environments. The phosphotransferase pathway is both widespread and relatively well conserved. However, reaction kinetics of these phosphotransferases remain poorly understood, their catalytic activities are suboptimal. In this study, a ZEA phosphotransferase, ZPH1101, was identified from subtilis 1101 using genome sequencing. product transformed by ZPH1101 as phosphorylated (ZEA-P) through LC-TOF-MS/MS analysis. experiments conducted on MCF-7 cells demonstrated that ZEA-P exhibited lower level estrogenic toxicity than ZEA. optimal conditions for were determined to be 45 °C pH 8.0. maximum velocity (Vmax), Michaelis constant (Km), (kcat) calculated fitting 16.40 μM·s-1·mg-1, 18.18 μM, 54.69 s-1, respectively. Furthermore, adding 1 mmol/L Fe2+ or Fe3+ system increased efficiency converting 100% relative containing solely ATP Mg2+, suggesting low concentrations can improve ZPH1101-mediated transformation This study contributes enzymatic removal broadens spectrum strain enzyme options available researchers detoxification efforts.

Language: Английский

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Direct conversion of various phosphate sources to a versatile P-X reagent [TBA][PO2X2] via redox-neutral halogenation

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 26, 2025

Abstract Inorganic phosphates hold significant potential as ideal natural building blocks, forming a fundamental basis for organic and biochemical synthesis. However, their limited solubility, inherent chemical stability, low reactivity pose substantial challenges to converting into organophosphates under mild conditions. This study introduces an efficient method the direct conversion of P(V)-X reagents, [TBA][PO 2 X ] (X = Cl, F), via redox-neutral halogenation process. utilizes cyanuric chloride (or fluoride) reagent, in combination with 1-formylpyrrolidine tetrabutylammonium (TBAC), ambient The approach enables effective various P(V) sources, including orthophosphates, pyrophosphoric acid, Na 3 P O 9 5 . Furthermore, we demonstrate synthetic utility P(V)-Cl reagent phosphorylation diverse -, S N - C- nucleophiles. Key advantages this process include use inexpensive readily available chemicals, avoidance high-energy redox reactions, generation reactive yet stable reagent.

Language: Английский

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Organic Reactivity Matters for the Emergence of Life: Kinetic Barriers and Molecular Diversity Are Suggested as Crucial Factors by Emerging Autonomous System Models

ChemSystemsChem, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Abstract The idea that organic chemistry can gradually self‐organize towards the emergence of life has been challenged by views considering most important driver should be existence a crucial thermodynamic disequilibrium. In this work, past are critically addressed and mechanism through which disequilibrium promote development organized systems is suggested. This analysis based on propensity carbon to form covalent bonds with other elements, usually corresponds deep energy wells generating high kinetic barriers hindering reactions. Potential associated considered as storing prepaid entropy loss within potential surface therefore constitute giving room for subsequent self‐organization processes. notion Kinetically Stable Thermodynamically Activated (KSTA) compounds gives rise possibility alternative pathways non‐linear autocatalytic As working in far‐from‐equilibrium context, like molecular machines, parameters determining how they proceed change, suggests interactions between fields machines could mutually beneficial.

Language: Английский

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Melatonin regulation of phase separation in Neuro-PASC: out-maneuvering Janus-faced amyloids

Exploration of neuroscience, Journal Year: 2025, Volume and Issue: 4

Published: March 24, 2025

The SAR-CoV-2 virus has evolved to co-exist with human hosts, albeit at a substantial energetic cost resulting in post-infection neurological manifestations [Neuro-post-acute sequelae of SARS-CoV-2 infection (PASC)] that significantly impact public health and economic productivity on global scale. One the main molecular mechanisms responsible for development Neuro-PASC, individuals all ages, is formation inadequate proteolysis/clearance phase-separated amyloid crystalline aggregates—a hallmark feature aging-related neurodegenerative disorders. Amyloidogenesis during viral persistence natural, inevitable, protective defense response exacerbated by SARS-CoV-2. Acting as chemical catalyst, accelerates hydrophobic collapse heterogeneous nucleation amorphous amyloids into stable β-sheet aggregates. clearance aggregates most effective slow wave sleep, when high levels adenosine triphosphate (ATP)—a biphasic modulator biomolecular condensates—and melatonin are available solubilize removal. dysregulation mitochondrial dynamics SARS-CoV-2, particular fusion fission homeostasis, impairs proper distinct subpopulations can remedy challenges created diversion substrates away from oxidative phosphorylation towards glycolysis support replication maintenance. subsequent reduction ATP inhibition synthesis sleep results incomplete brain aggregates, leading commonly associated age-related Exogenous not only prevents dysfunction but also elevates production, effectively augmenting solubilizing effect moiety ensure timely, optimal disaggregation pathogenic prevention attenuation Neuro-PASC.

Language: Английский

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Abiotic Acyl Transfer Cascades Driven by Aminoacyl Phosphate Esters and Self-Assembly

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(43), P. 29621 - 29629

Published: Oct. 17, 2024

Biochemical acyl transfer cascades, such as those initiated by the adenylation of carboxylic acids, are central to various biological processes, including protein synthesis and fatty acid metabolism. Designing cascade reactions in aqueous media remains challenging due need control multiple, sequential a single pot manage stability reactive intermediates. Herein, we developed abiotic cascades using aminoacyl phosphate esters, synthetic counterparts adenylates, drive chemical self-assembly pot. We demonstrated that structural elements amino side chains (aromatic versus aliphatic) significantly influence reactivity half-lives ranging from hours days. This behavior, turn, affects number couplings can achieve network propensity activated intermediate structures. The constructed bifunctional peptide substrates featuring chain nucleophiles. Specifically, aromatic acids facilitate formation transient thioesters, which preorganized into spherical aggregates further couple chimeric assemblies composed esters thioesters. In contrast, aliphatic lack ability form structures, predominantly undergo hydrolysis, bypassing transformations after thioester formation. Additionally, mixtures containing multiple substrates, achieved selective product following distinct pathway favors subsequent through changes self-assembly. By coupling with molecules varying time scales, reaction clocks lifetimes dynamics, facilitating precise temporal regulation.

Language: Английский

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The Many‐Chemicals Problem of Systems Chemistry

ChemSystemsChem, Journal Year: 2024, Volume and Issue: 6(5)

Published: May 22, 2024

Abstract An E. coli cell contains ~2500 different chemicals which combine into an ordered biochemical reaction network out of emerges a living system. A chemist taking 2500 from laboratory chemical cabinet and combining them together will likely cause explosive disaster produce intractable sludge. Systems Chemistry aspires to construct systems whose complexity rivals that life. However, do this we need learn how hundreds or thousands form functional system without descending disordered This is the Many‐Chemicals Problem Chemistry. I explore key strategy life employs overcome challenge. Namely, combination kinetically stable thermodynamically activated molecules (e. g. ATP) with enzyme catalysts histidine kinases). suggest could have begun at origin Finally, assess implications for it enable chemists

Language: Английский

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Abiotic Acyl Transfer Cascades Driven by Aminoacyl Phosphate Esters and Self-Assembly

Published: Aug. 5, 2024

Biochemical acyl transfer cascades, such as those initiated by the adenylation of carboxylic acids, are central to various biological processes, including protein synthesis and fatty acid metabolism. Designing aqueous cascades outside biology remains challenging due need control multiple, sequential reactions in a single pot manage stability reactive intermediates. Herein, we developed abiotic using aminoacyl phosphate esters, synthetic counterparts adenylates, drive chemical self-assembly pot. We demonstrated that structural elements amino side chains (aromatic versus aliphatic) significantly influence reactivity half-lives ranging from hours days. This behavior, turn, affects number couplings can achieve network propensity activated intermediate structures. The constructed bifunctional peptide substrates featuring chain nucleophiles. Specifically, aromatic acids facilitate formation transient thioesters, which preorganized into spherical aggregates further couple chimeric assemblies composed esters thioesters. In contrast, aliphatic lack ability form structures, predominantly lead hydrolysis, bypassing elongation after thioester formation. Additionally, mixtures containing multiple substrates, achieved selective product following distinct pathway favors through self-assembly. By coupling molecules with varying timescales, reaction clocks lifetimes dynamics, thereby facilitating precise temporal regulation.

Language: Английский

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Cost-effective phosphates redox-neutral transformation to bench-stable phosphorylation precursor

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 20, 2024

Modern synthesis methods of organophosphorus heavily rely on white phosphorus and its (oxy)chlorination reagents. Phosphates have the potential to serve as perfect natural building blocks, forming basis for organic biochemical syntheses. However, poor solubility, high stability, low reactivity make it challenging transformation phosphates active reagents under mild conditions. Here we show an efficient conversion in which various phosphate sources are directly transformed into [TBA][PO2X2] (X = Cl, F) phosphorylation through a redox-neutral process by using cyanuric chloride 1-formylpyrrolidine presence tetrabutylammonium at ambient Key features this involve utilization cost-effective readily available chemicals, circumventing need redox reactions with high-energy reactive yet stable P(V)-reagent. In comparison known precursor, [PO2X2]- salts bench-stable, easy handle, affording compounds before substrates.

Language: Английский

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