Journal articles: 'Protometabolism'

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de Duve, Christian. "From protometabolism to metabolism." Origins of life and evolution of the biosphere 24, no. 2-4 (June 1994): 346–62. http://dx.doi.org/10.1007/bf02627949.

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Broecker, Felix. "Genome Evolution from Random Ligation of RNAs of Autocatalytic Sets." International Journal of Molecular Sciences 22, no. 24 (December 16, 2021): 13526. http://dx.doi.org/10.3390/ijms222413526.

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The evolutionary origin of the genome remains elusive. Here, I hypothesize that its first iteration, the protogenome, was a multi-ribozyme RNA. It evolved, likely within liposomes (the protocells) forming in dry-wet cycling environments, through the random fusion of ribozymes by a ligase and was amplified by a polymerase. The protogenome thereby linked, in one molecule, the information required to seed the protometabolism (a combination of RNA-based autocatalytic sets) in newly forming protocells. If this combination of autocatalytic sets was evolutionarily advantageous, the protogenome would have amplified in a population of multiplying protocells. It likely was a quasispecies with redundant information, e.g., multiple copies of one ribozyme. As such, new functionalities could evolve, including a genetic code. Once one or more components of the protometabolism were templated by the protogenome (e.g., when a ribozyme was replaced by a protein enzyme), and/or addiction modules evolved, the protometabolism became dependent on the protogenome. Along with increasing fidelity of the RNA polymerase, the protogenome could grow, e.g., by incorporating additional ribozyme domains. Finally, the protogenome could have evolved into a DNA genome with increased stability and storage capacity. I will provide suggestions for experiments to test some aspects of this hypothesis, such as evaluating the ability of ribozyme RNA polymerases to generate random ligation products and testing the catalytic activity of linked ribozyme domains.

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Pratt, Andrew J. "Prebiological Evolution and the Metabolic Origins of Life." Artificial Life 17, no. 3 (July 2011): 203–17. http://dx.doi.org/10.1162/artl_a_00032.

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The chemoton model of cells posits three subsystems: metabolism, compartmentalization, and information. A specific model for the prebiological evolution of a reproducing system with rudimentary versions of these three interdependent subsystems is presented. This is based on the initial emergence and reproduction of autocatalytic networks in hydrothermal microcompartments containing iron sulfide. The driving force for life was catalysis of the dissipation of the intrinsic redox gradient of the planet. The codependence of life on iron and phosphate provides chemical constraints on the ordering of prebiological evolution. The initial protometabolism was based on positive feedback loops associated with in situ carbon fixation in which the initial protometabolites modified the catalytic capacity and mobility of metal-based catalysts, especially iron-sulfur centers. A number of selection mechanisms, including catalytic efficiency and specificity, hydrolytic stability, and selective solubilization, are proposed as key determinants for autocatalytic reproduction exploited in protometabolic evolution. This evolutionary process led from autocatalytic networks within preexisting compartments to discrete, reproducing, mobile vesicular protocells with the capacity to use soluble sugar phosphates and hence the opportunity to develop nucleic acids. Fidelity of information transfer in the reproduction of these increasingly complex autocatalytic networks is a key selection pressure in prebiological evolution that eventually leads to the selection of nucleic acids as a digital information subsystem and hence the emergence of fully functional chemotons capable of Darwinian evolution.

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Kitadai, Norio, Ryuhei Nakamura, Masahiro Yamamoto, Ken Takai, Naohiro Yoshida, and Yoshi Oono. "Metals likely promoted protometabolism in early ocean alkaline hydrothermal systems." Science Advances 5, no. 6 (June 2019): eaav7848. http://dx.doi.org/10.1126/sciadv.aav7848.

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One of the most plausible scenarios of the origin of life assumes the preceding prebiotic autotrophic metabolism in sulfide-rich hydrothermal vent environments. However, geochemical mechanisms to harness the reductive power provided by hydrothermal systems remain to be elucidated. Here, we show that, under a geoelectrochemical condition realizable in the early ocean hydrothermal systems, several metal sulfides (FeS, Ag2S, CuS, and PbS) undergo hour- to day-scale conversion to the corresponding metals at ≤−0.7 V (versus the standard hydrogen electrode). The electrochemically produced FeS-Fe0 assemblage promoted various reactions including certain steps in the reductive tricarboxylic acid cycle with efficiencies far superior to those due to pure FeS. The threshold potential is readily generated in the H2-rich alkaline hydrothermal systems that were probably ubiquitous on the Hadean seafloor. Thus, widespread metal production and metal-sustained primordial metabolism were likely to occur as a natural consequence of the active hydrothermal processes on the Hadean Earth.

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Hagan, William J. "Uracil-Catalyzed Synthesis of Acetyl Phosphate: A Photochemical Driver for Protometabolism." ChemBioChem 11, no. 3 (February 15, 2010): 383–87. http://dx.doi.org/10.1002/cbic.200900433.

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Patel, Bhavesh H., Claudia Percivalle, Dougal J. Ritson, Colm D. Duffy, and John D. Sutherland. "Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism." Nature Chemistry 7, no. 4 (March 16, 2015): 301–7. http://dx.doi.org/10.1038/nchem.2202.

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Monreal Santiago, Guillermo, Kai Liu, Wesley R. Browne, and Sijbren Otto. "Emergence of light-driven protometabolism on recruitment of a photocatalytic cofactor by a self-replicator." Nature Chemistry 12, no. 7 (June 26, 2020): 603–7. http://dx.doi.org/10.1038/s41557-020-0494-4.

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Emond, Matthieu, Thomas Le Saux, Jean-Francois Allemand, Philippe Pelupessy, Raphaël Plasson, and Ludovic Jullien. "Energy Propagation Through a Protometabolism Leading to the Local Emergence of Singular Stationary Concentration Profiles." Chemistry - A European Journal 18, no. 45 (September 25, 2012): 14375–83. http://dx.doi.org/10.1002/chem.201201974.

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Zhou, Xianfeng, Punam Dalai, and Nita Sahai. "Semipermeable Mixed Phospholipid-Fatty Acid Membranes Exhibit K+/Na+ Selectivity in the Absence of Proteins." Life 10, no. 4 (April 14, 2020): 39. http://dx.doi.org/10.3390/life10040039.

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Two important ions, K+ and Na+, are unequally distributed across the contemporary phospholipid-based cell membrane because modern cells evolved a series of sophisticated protein channels and pumps to maintain ion gradients. The earliest life-like entities or protocells did not possess either ion-tight membranes or ion pumps, which would result in the equilibration of the intra-protocellular K+/Na+ ratio with that in the external environment. Here, we show that the most primitive protocell membranes composed of fatty acids, that were initially leaky, would eventually become less ion permeable as their membranes evolved towards having increasing phospholipid contents. Furthermore, these mixed fatty acid-phospholipid membranes selectively retain K+ but allow the passage of Na+ out of the cell. The K+/Na+ selectivity of these mixed fatty acid-phospholipid semipermeable membranes suggests that protocells at intermediate stages of evolution could have acquired electrochemical K+/Na+ ion gradients in the absence of any macromolecular transport machinery or pumps, thus potentially facilitating rudimentary protometabolism.

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Helman, Daniel S., and Matthew Retallack. "Electrochemical cells from water ice? Preliminary methods and results." PLOS ONE 18, no. 8 (August 24, 2023): e0285507. http://dx.doi.org/10.1371/journal.pone.0285507.

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Electrochemical cells from ice will be an important seasonal addition to power generation in cold regions. We demonstrate power generation on the order of 0.1 mW at 0.3 V and 0.13 m2 surface area using an electrochemical cell with 2% HCl providing a pH gradient in ice, and suggest a solar add-on effect due to temperature changes under direct sunlight. Different models are discussed, and data are presented related to different additives: (1) solutes such as NaCl and monopotassium phosphate; (2) pH modifying agents such as acids and bases; (3) particulate suspensions with kaolinite and other substances. The results are positive and suggest viable use of electrochemical cells from ice with low fabrication costs and safe environmental impact for ephemeral power generation, especially with future material improvements and refinement of technique. Current research in this nascent field is also briefly introduced. The model presented has implications both for power systems and for biology: an icy-worlds hypothesis for the origin of life suggests a protometabolism with an ice-based pH gradient.

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Pinna, Silvana, Cäcilia Kunz, Aaron Halpern, Stuart A. Harrison, Sean F. Jordan, John Ward, Finn Werner, and Nick Lane. "A prebiotic basis for ATP as the universal energy currency." PLOS Biology 20, no. 10 (October 4, 2022): e3001437. http://dx.doi.org/10.1371/journal.pbio.3001437.

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ATP is universally conserved as the principal energy currency in cells, driving metabolism through phosphorylation and condensation reactions. Such deep conservation suggests that ATP arose at an early stage of biochemical evolution. Yet purine synthesis requires 6 phosphorylation steps linked to ATP hydrolysis. This autocatalytic requirement for ATP to synthesize ATP implies the need for an earlier prebiotic ATP equivalent, which could drive protometabolism before purine synthesis. Why this early phosphorylating agent was replaced, and specifically with ATP rather than other nucleoside triphosphates, remains a mystery. Here, we show that the deep conservation of ATP might reflect its prebiotic chemistry in relation to another universally conserved intermediate, acetyl phosphate (AcP), which bridges between thioester and phosphate metabolism by linking acetyl CoA to the substrate-level phosphorylation of ADP. We confirm earlier results showing that AcP can phosphorylate ADP to ATP at nearly 20% yield in water in the presence of Fe3+ ions. We then show that Fe3+ and AcP are surprisingly favoured. A wide range of prebiotically relevant ions and minerals failed to catalyse ADP phosphorylation. From a panel of prebiotic phosphorylating agents, only AcP, and to a lesser extent carbamoyl phosphate, showed any significant phosphorylating potential. Critically, AcP did not phosphorylate any other nucleoside diphosphate. We use these data, reaction kinetics, and molecular dynamic simulations to infer a possible mechanism. Our findings might suggest that the reason ATP is universally conserved across life is that its formation is chemically favoured in aqueous solution under mild prebiotic conditions.

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Basak, Shibaji, Serge Nader, and Sheref S. Mansy. "Protometabolic Reduction of NAD+ with α-Keto Acids." JACS Au 1, no. 4 (March 12, 2021): 371–74. http://dx.doi.org/10.1021/jacsau.0c00124.

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Omran, Arthur, Asbell Gonzalez, Cesar Menor-Salvan, Michael Gaylor, Jing Wang, Jerzy Leszczynski, and Tian Feng. "Serpentinization-Associated Mineral Catalysis of the Protometabolic Formose System." Life 13, no. 6 (May 31, 2023): 1297. http://dx.doi.org/10.3390/life13061297.

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The formose reaction is a plausible prebiotic chemistry, famed for its production of sugars. In this work, we demonstrate that the Cannizzaro process is the dominant process in the formose reaction under many different conditions, thus necessitating a catalyst for the formose reaction under various environmental circumstances. The investigated formose reactions produce primarily organic acids associated with metabolism, a protometabolic system, and yield very little sugar left over. This is due to many of the acids forming from the degradation and Cannizaro reactions of many of the sugars produced during the formose reaction. We also show the heterogeneous Lewis-acid-based catalysis of the formose reaction by mineral systems associated with serpentinization. The minerals that showed catalytic activity include olivine, serpentinite, and calcium, and magnesium minerals including dolomite, calcite, and our Ca/Mg-chemical gardens. In addition, computational studies were performed for the first step of the formose reaction to investigate the reaction of formaldehyde, to either form methanol and formic acid under a Cannizzaro reaction or to react to form glycolaldehyde. Here, we postulate that serpentinization is therefore the startup process necessary to kick off a simple proto metabolic system—the formose protometabolic system.

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Harrison, Stuart A., William L. Webb, Hanadi Rammu, and Nick Lane. "Prebiotic Synthesis of Aspartate Using Life’s Metabolism as a Guide." Life 13, no. 5 (May 12, 2023): 1177. http://dx.doi.org/10.3390/life13051177.

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

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Yadav, Mahipal, Sunil Pulletikurti, Jayasudhan R. Yerabolu, and Ramanarayanan Krishnamurthy. "Cyanide as a primordial reductant enables a protometabolic reductive glyoxylate pathway." Nature Chemistry 14, no. 2 (February 2022): 170–78. http://dx.doi.org/10.1038/s41557-021-00878-w.

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Dalai, Punam, and Nita Sahai. "A Model Protometabolic Pathway across Protocell Membranes Assisted by Photocatalytic Minerals." Journal of Physical Chemistry C 124, no. 2 (December 23, 2019): 1469–77. http://dx.doi.org/10.1021/acs.jpcc.9b10127.

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Piedrafita, Gabriel, Kepa Ruiz-Mirazo, Pierre-Alain Monnard, Athel Cornish-Bowden, and Francisco Montero. "Viability Conditions for a Compartmentalized Protometabolic System: A Semi-Empirical Approach." PLoS ONE 7, no. 6 (June 27, 2012): e39480. http://dx.doi.org/10.1371/journal.pone.0039480.

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Tian, Tian, Xin-Yi Chu, Yi Yang, Xuan Zhang, Ye-Mao Liu, Jun Gao, Bin-Guang Ma, and Hong-Yu Zhang. "Phosphates as Energy Sources to Expand Metabolic Networks." Life 9, no. 2 (May 22, 2019): 43. http://dx.doi.org/10.3390/life9020043.

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Phosphates are essential for modern metabolisms. A recent study reported a phosphate-free metabolic network and suggested that thioesters, rather than phosphates, could alleviate thermodynamic bottlenecks of network expansion. As a result, it was considered that a phosphorus-independent metabolism could exist before the phosphate-based genetic coding system. To explore the origin of phosphorus-dependent metabolism, the present study constructs a protometabolic network that contains phosphates prebiotically available using computational systems biology approaches. It is found that some primitive phosphorylated intermediates could greatly alleviate thermodynamic bottlenecks of network expansion. Moreover, the phosphorus-dependent metabolic network exhibits several ancient features. Taken together, it is concluded that phosphates played a role as important as that of thioesters during the origin and evolution of metabolism. Both phosphorus and sulfur are speculated to be critical to the origin of life.

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Maury, Carl Peter J. "Amyloid and the origin of life: self-replicating catalytic amyloids as prebiotic informational and protometabolic entities." Cellular and Molecular Life Sciences 75, no. 9 (March 17, 2018): 1499–507. http://dx.doi.org/10.1007/s00018-018-2797-9.

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Mavelli, Fabio, and Kepa Ruiz-Mirazo. "Stochastic simulations of minimal self-reproducing cellular systems." Philosophical Transactions of the Royal Society B: Biological Sciences 362, no. 1486 (May 9, 2007): 1789–802. http://dx.doi.org/10.1098/rstb.2007.2071.

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This paper is a theoretical attempt to gain insight into the problem of how self-assembling vesicles (closed bilayer structures) could progressively turn into minimal self-producing and self-reproducing cells, i.e. into interesting candidates for (proto)biological systems. With this aim, we make use of a recently developed object-oriented platform to carry out stochastic simulations of chemical reaction networks that take place in dynamic cellular compartments. We apply this new tool to study the behaviour of different minimal cell models, making realistic assumptions about the physico-chemical processes and conditions involved (e.g. thermodynamic equilibrium/non-equilibrium, variable volume-to-surface relationship, osmotic pressure, solute diffusion across the membrane due to concentration gradients, buffering effect). The new programming platform has been designed to analyse not only how a single protometabolic cell could maintain itself, grow or divide, but also how a collection of these cells could ‘evolve’ as a result of their mutual interactions in a common environment.

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Krishnamurthy, Ramanarayanan, and Charles L. Liotta. "The potential of glyoxylate as a prebiotic source molecule and a reactant in protometabolic pathways—The glyoxylose reaction." Chem 9, no. 4 (April 2023): 784–97. http://dx.doi.org/10.1016/j.chempr.2023.03.007.

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Jia, Tony Z., Kuhan Chandru, Yayoi Hongo, Rehana Afrin, Tomohiro Usui, Kunihiro Myojo, and H. James Cleaves. "Membraneless polyester microdroplets as primordial compartments at the origins of life." Proceedings of the National Academy of Sciences 116, no. 32 (July 22, 2019): 15830–35. http://dx.doi.org/10.1073/pnas.1902336116.

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Compartmentalization was likely essential for primitive chemical systems during the emergence of life, both for preventing leakage of important components, i.e., genetic materials, and for enhancing chemical reactions. Although life as we know it uses lipid bilayer-based compartments, the diversity of prebiotic chemistry may have enabled primitive living systems to start from other types of boundary systems. Here, we demonstrate membraneless compartmentalization based on prebiotically available organic compounds, α-hydroxy acids (αHAs), which are generally coproduced along with α-amino acids in prebiotic settings. Facile polymerization of αHAs provides a model pathway for the assembly of combinatorially diverse primitive compartments on early Earth. We characterized membraneless microdroplets generated from homo- and heteropolyesters synthesized from drying solutions of αHAs endowed with various side chains. These compartments can preferentially and differentially segregate and compartmentalize fluorescent dyes and fluorescently tagged RNA, providing readily available compartments that could have facilitated chemical evolution by protecting, exchanging, and encapsulating primitive components. Protein function within and RNA function in the presence of certain droplets is also preserved, suggesting the potential relevance of such droplets to various origins of life models. As a lipid amphiphile can also assemble around certain droplets, this further shows the droplets’ potential compatibility with and scaffolding ability for nascent biomolecular systems that could have coexisted in complex chemical systems. These model compartments could have been more accessible in a “messy” prebiotic environment, enabling the localization of a variety of protometabolic and replication processes that could be subjected to further chemical evolution before the advent of the Last Universal Common Ancestor.

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Ruiz-Bermejo, Marta, José Luis de la Fuente, Cristina Pérez-Fernández, and Eva Mateo-Martí. "A Comprehensive Review of HCN-Derived Polymers." Processes 9, no. 4 (March 29, 2021): 597. http://dx.doi.org/10.3390/pr9040597.

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HCN-derived polymers are a heterogeneous group of complex substances synthesized from pure HCN; from its salts; from its oligomers, specifically its trimer and tetramer, amino-nalono-nitrile (AMN) and diamino-maleo-nitrile (DAMN), respectively; or from its hydrolysis products, such as formamide, under a wide range of experimental conditions. The characteristics and properties of HCN-derived polymers depend directly on the synthetic conditions used for their production and, by extension, their potential applications. These puzzling systems have been known mainly in the fields of prebiotic chemistry and in studies on the origins of life and astrobiology since the first prebiotic production of adenine by Oró in the early years of the 1960s. However, the first reference regarding their possible role in prebiotic chemistry was mentioned in the 19th century by Pflüger. Currently, HCN-derived polymers are considered keys in the formation of the first and primeval protometabolic and informational systems, and they may be among the most readily formed organic macromolecules in the solar system. In addition, HCN-derived polymers have attracted a growing interest in materials science due to their potential biomedical applications as coatings and adhesives; they have also been proposed as valuable models for multifunctional materials with emergent properties such as semi-conductivity, ferroelectricity, catalysis and photocatalysis, and heterogeneous organo-synthesis. However, the real structures and the formation pathways of these fascinating substances have not yet been fully elucidated; several models based on either computational approaches or spectroscopic and analytical techniques have endeavored to shed light on their complete nature. In this review, a comprehensive perspective of HCN-derived polymers is presented, taking into account all the aspects indicated above.

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Nader, Serge, Lorenzo Sebastianelli, and Sheref S. Mansy. "Protometabolism as out-of-equilibrium chemistry." Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 380, no. 2227 (May 23, 2022). http://dx.doi.org/10.1098/rsta.2020.0423.

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It is common to compare life with machines. Both consume fuel and release waste to run. In biology, the engine that drives the living system is referred to as metabolism. However, attempts at deciphering the origins of metabolism do not focus on this energetic relationship that sustains life but rather concentrate on nonenzymatic reactions that produce all the intermediates of an extant metabolic pathway. Such an approach is akin to studying the molecules produced from the burning of coal instead of deciphering how the released energy drives the movement of pistons and ultimately the train when investigating the mechanisms behind locomotion. Theories that do explicitly invoke geological chemical gradients to drive metabolism most frequently feature hydrothermal vent conditions, but hydrothermal vents are not the only regions of the early Earth that could have provided the fuel necessary to sustain the Earth's first (proto)cells. Here, we give examples of prior reports on protometabolism and highlight how more recent investigations of out-of-equilibrium systems may point to alternative scenarios more consistent with the majority of prebiotic chemistry data accumulated thus far. This article is part of the theme issue ‘Emergent phenomena in complex physical and socio-technical systems: from cells to societies’.

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Reja, Antara, Sumit Pal, Kishalay Mahato, Baishakhi Saha, Massimo Delle Piane, Giovanni M. Pavan, and Dibyendu Das. "Emergence of Photomodulated Protometabolism by Short Peptide-Based Assemblies." Journal of the American Chemical Society, September 14, 2023. http://dx.doi.org/10.1021/jacs.3c08158.

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Kitadai, Norio, Ryuhei Nakamura, Masahiro Yamamoto, Satoshi Okada, Wataru Takahagi, Yuko Nakano, Yoshio Takahashi, Ken Takai, and Yoshi Oono. "Thioester synthesis through geoelectrochemical CO2 fixation on Ni sulfides." Communications Chemistry 4, no. 1 (March 17, 2021). http://dx.doi.org/10.1038/s42004-021-00475-5.

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AbstractA prevailing scenario of the origin of life postulates thioesters as key intermediates in protometabolism, but there is no experimental support for the prebiotic CO2 fixation routes to thioesters. Here we demonstrate that, under a simulated geoelectrochemical condition in primordial ocean hydrothermal systems (–0.6 to –1.0 V versus the standard hydrogen electrode), nickel sulfide (NiS) gradually reduces to Ni0, while accumulating surface-bound carbon monoxide (CO) due to CO2 electroreduction. The resultant partially reduced NiS realizes thioester (S-methyl thioacetate) formation from CO and methanethiol even at room temperature and neutral pH with the yield up to 35% based on CO. This thioester formation is not inhibited, or even improved, by 50:50 coprecipitation of NiS with FeS or CoS (the maximum yields; 27 or 56%, respectively). Such a simple thioester synthesis likely occurred in Hadean deep-sea vent environments, setting a stage for the autotrophic origin of life.

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Nogal, Noemí, Marcos Sanz-Sánchez, Sonia Vela-Gallego, Kepa Ruiz-Mirazo, and Andrés de la Escosura. "The protometabolic nature of prebiotic chemistry." Chemical Society Reviews, 2023. http://dx.doi.org/10.1039/d3cs00594a.

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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 as the boundary conditions under which they would become protometabolic.

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Zhao, Weishu, Bozitao Zhong, Lirong Zheng, Pan Tan, Yinzhao Wang, Hao Leng, Nicolas de Souza, Zhuo Liu, Liang Hong, and Xiang Xiao. "Proteome-wide 3D structure prediction provides insights into the ancestral metabolism of ancient archaea and bacteria." Nature Communications 13, no. 1 (December 21, 2022). http://dx.doi.org/10.1038/s41467-022-35523-8.

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AbstractAncestral metabolism has remained controversial due to a lack of evidence beyond sequence-based reconstructions. Although prebiotic chemists have provided hints that metabolism might originate from non-enzymatic protometabolic pathways, gaps between ancestral reconstruction and prebiotic processes mean there is much that is still unknown. Here, we apply proteome-wide 3D structure predictions and comparisons to investigate ancestorial metabolism of ancient bacteria and archaea, to provide information beyond sequence as a bridge to the prebiotic processes. We compare representative bacterial and archaeal strains, which reveal surprisingly similar physiological and metabolic characteristics via microbiological and biophysical experiments. Pairwise comparison of protein structures identify the conserved metabolic modules in bacteria and archaea, despite interference from overly variable sequences. The conserved modules (for example, middle of glycolysis, partial TCA, proton/sulfur respiration, building block biosynthesis) constitute the basic functions that possibly existed in the archaeal-bacterial common ancestor, which are remarkably consistent with the experimentally confirmed protometabolic pathways. These structure-based findings provide a new perspective to reconstructing the ancestral metabolism and understanding its origin, which suggests high-throughput protein 3D structure prediction is a promising approach, deserving broader application in future ancestral exploration.

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Dalai, Punam, and Nita Sahai. "A Model Protometabolic Pathway Across Protocell Membranes Assisted by Photocatalytic Minerals." Journal of Physical Chemistry B, December 23, 2019. http://dx.doi.org/10.1021/acs.jpcb.9b10127.

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Moreno, Abel, and Colin Bonduelle. "New Insights on the Chemical Origin of Life: The Role of Aqueous Polymerization of N‐carboxyanhydrides (NCA)." ChemPlusChem, January 24, 2024. http://dx.doi.org/10.1002/cplu.202300492.

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AbstractAt the origin, the emergence of proteins was based on crucial prebiotic stages in which simple amino acids‐based building blocks spontaneously evolved from the prebiotic soup into random proto‐polymers called protoproteins. Despite advances in modern peptide synthesis, these prebiotic chemical routes to protoproteins remain puzzling. We discuss in this perspective how polymer science and systems chemistry are reaching a point of convergence in which simple monomers called N‐carboxyanhydrides would be able to form such protoproteins via the emergence of a protometabolic cycle involving aqueous polymerization and featuring macromolecular Darwinism behavior.

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Clay, Alyssa P., Rachel E. Cooke, Ravi Kumar, Mahipal Yadav, Ramanarayanan Krishnamurthy, and Greg Springsteen. "A Plausible Prebiotic One‐Pot Synthesis of Orotate and Pyruvate Suggestive of Common Protometabolic Pathways." Angewandte Chemie 134, no. 11 (January 26, 2022). http://dx.doi.org/10.1002/ange.202112572.

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Clay, Alyssa P., Rachel E. Cooke, Ravi Kumar, Mahipal Yadav, Ramanarayanan Krishnamurthy, and Greg Springsteen. "A Plausible Prebiotic One‐Pot Synthesis of Orotate and Pyruvate Suggestive of Common Protometabolic Pathways." Angewandte Chemie International Edition 61, no. 11 (January 27, 2022). http://dx.doi.org/10.1002/anie.202112572.

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Springsteen, Greg, Jayasudhan Reddy Yerabolu, Julia Nelson, Chandler Joel Rhea, and Ramanarayanan Krishnamurthy. "Linked cycles of oxidative decarboxylation of glyoxylate as protometabolic analogs of the citric acid cycle." Nature Communications 9, no. 1 (January 8, 2018). http://dx.doi.org/10.1038/s41467-017-02591-0.

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Ter-Ovanessian, Louis M. P., Jean-François Lambert, and Marie-Christine Maurel. "Building the uracil skeleton in primitive ponds at the origins of life: carbamoylation of aspartic acid." Scientific Reports 12, no. 1 (November 10, 2022). http://dx.doi.org/10.1038/s41598-022-21272-7.

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AbstractA large set of nucleobases and amino acids is found in meteorites, implying that several chemical reservoirs are present in the solar system. The “geochemical continuity” hypothesis explores how protometabolic paths developed from so-called “bricks” in an enzyme-free prebiotic world and how they affected the origins of life. In the living cell, the second step of synthesizing uridine and cytidine RNA monomers is a carbamoyl transfer from a carbamoyl donor to aspartic acid. Here we compare two enzyme-free scenarios: aqueous and mineral surface scenarios in a thermal range up to 250 °C. Both processes could have happened in ponds under open atmosphere on the primeval Earth. Carbamoylation of aspartic acid with cyanate in aqueous solutions at 25 °C gives high N-carbamoyl aspartic acid yields within 16 h. It is important to stress that, while various molecules could be efficient carbamoylating agents according to thermodynamics, kinetics plays a determining role in selecting prebiotically possible pathways.

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Harrison, Stuart A., Hanadi Rammu, Feixue Liu, Aaron Halpern, Raquel Nunes Palmeira, and Nick Lane. "Life as a Guide to its Own Origins." Annual Review of Ecology, Evolution, and Systematics 54, no. 1 (August 22, 2023). http://dx.doi.org/10.1146/annurev-ecolsys-110421-101509.

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The origin of life entails a continuum from simple prebiotic chemistry to cells with genes and molecular machines. Using life as a guide to this continuum, we consider how selection could promote increased complexity before the emergence of genes. Structured, far-from-equilibrium environments such as hydrothermal systems drive the reaction between CO2 and H2 to form organics that self-organize into protocells. CO2 fixation within protocells generates a reaction network with a topology that prefigures the universal core of metabolism. Positive feedback loops amplify flux through this network, giving a metabolic heredity that promotes growth. Patterns in the genetic code show that genes and proteins arose through direct biophysical interactions between amino acids and nucleotides in this protometabolic network. Random genetic sequences template nonrandom peptides, producing selectable function in growing protocells. This context-dependent emergence of information gives rise seamlessly to an autotrophic last universal common ancestor. Expected final online publication date for the Annual Review of Ecology, Evolution, and Systematics, Volume 54 is November 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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36

Nunes Palmeira, Raquel, Marco Colnaghi, Stuart A. Harrison, Andrew Pomiankowski, and Nick Lane. "The limits of metabolic heredity in protocells." Proceedings of the Royal Society B: Biological Sciences 289, no. 1986 (November 9, 2022). http://dx.doi.org/10.1098/rspb.2022.1469.

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The universal core of metabolism could have emerged from thermodynamically favoured prebiotic pathways at the origin of life. Starting with H 2 and CO 2 , the synthesis of amino acids and mixed fatty acids, which self-assemble into protocells, is favoured under warm anoxic conditions. Here, we address whether it is possible for protocells to evolve greater metabolic complexity, through positive feedbacks involving nucleotide catalysis. Using mathematical simulations to model metabolic heredity in protocells, based on branch points in protometabolic flux, we show that nucleotide catalysis can indeed promote protocell growth. This outcome only occurs when nucleotides directly catalyse CO 2 fixation. Strong nucleotide catalysis of other pathways (e.g. fatty acids and amino acids) generally unbalances metabolism and slows down protocell growth, and when there is competition between catalytic functions cell growth collapses. Autocatalysis of nucleotide synthesis can promote growth but only if nucleotides also catalyse CO 2 fixation; autocatalysis alone leads to the accumulation of nucleotides at the expense of CO 2 fixation and protocell growth rate. Our findings offer a new framework for the emergence of greater metabolic complexity, in which nucleotides catalyse broad-spectrum processes such as CO 2 fixation, hydrogenation and phosphorylation important to the emergence of genetic heredity at the origin of life.

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Ter-Ovanessian, Louis M. P., Baptiste Rigaud, Alberto Mezzetti, Jean-François Lambert, and Marie-Christine Maurel. "Carbamoyl phosphate and its substitutes for the uracil synthesis in origins of life scenarios." Scientific Reports 11, no. 1 (September 29, 2021). http://dx.doi.org/10.1038/s41598-021-98747-6.

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AbstractThe first step of pyrimidine synthesis along the orotate pathway is studied to test the hypothesis of geochemical continuity of protometabolic pathways at the origins of life. Carbamoyl phosphate (CP) is the first high-energy building block that intervenes in the in vivo synthesis of the uracil ring of UMP. Thus, the likelihood of its occurrence in prebiotic conditions is investigated herein. The evolution of carbamoyl phosphate in water and in ammonia aqueous solutions without enzymes was characterised using ATR-IR, 31P and 13C spectroscopies. Carbamoyl phosphate initially appears stable in water at ambient conditions before transforming to cyanate and carbamate/hydrogenocarbonate species within a matter of hours. Cyanate, less labile than CP, remains a potential carbamoylating agent. In the presence of ammonia, CP decomposition occurs more rapidly and generates urea. We conclude that CP is not a likely prebiotic reagent by itself. Alternatively, cyanate and urea may be more promising substitutes for CP, because they are both “energy-rich” (high free enthalpy molecules in aqueous solutions) and kinetically inert regarding hydrolysis. Energy-rich inorganic molecules such as trimetaphosphate or phosphoramidates were also explored for their suitability as sources of carbamoyl phosphate. Although these species did not generate CP or other carbamoylating agents, they exhibited energy transduction, specifically the formation of high-energy P–N bonds. Future efforts should aim to evaluate the role of carbamoylating agents in aspartate carbamoylation, which is the following reaction in the orotate pathway.

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Journal articles on the topic 'Protometabolism'

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