Auswahl der wissenschaftlichen Literatur zum Thema „Protometabolism“

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.

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.

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.

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.

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.

Understanding the origin of life is one of the foremost challenges for science. Despite the immense diversity displayed by biology on the macroscopic scale, cellular biochemistry is at its most fundamental level remarkably uniform. Recognising the minimal elements of biochemistry required for a living system represents one task within origins of life research, whereas the other is understanding the organic chemistry which could have led to their spontaneous organisation on the abiotic Earth. Significant attention has been paid to the prebiotic generation and assembly of the components of nucleic acids resulting in the demonstration of important prebiotic syntheses and in the uncovering of various key problems which have seeded much informative discussion within the prebiotic community. However, experimental investigations into the assembly of key sets of ubiquitous metabolites have been comparatively lacking and will be necessary to assess the relevance of central metabolic pathways to the earliest stages in the development of life. Presented herein are investigations into the prebiotic chemistry of a selection of small molecules central to one of the most fundamental and highly conserved metabolic pathways found in biology; triose glycolysis. By utilising a prebiotically relevant method of specifically generating aldehyde-2-phosphates from simple sugar precursors, it has been shown that several intermediates common to glycolysis can be generated in high yield under mild, aqueous conditions in a simple step-wise sequence which culminates in the generation (for the first time under prebiotically relevant conditions) of the highest-energy organophosphate utilised by nature; phosphoenolpyruvate. Based on the demonstrated transformations, a potentially prebiotic network of glycolytic reactions is proposed, sharing common precursors and reaction conditions with important existing work within the field concerning the generation of nucleotides, amino-acids and lipids. The predisposition of hydroxy-aldehydes to glycolytically important transformations and the relationship of the proposed prebiotic network to extant glycolysis is discussed.

La thèse aborde différentes questions de chimie prébiotique dans le contexte de l’origine de la vie par une approche de chimie systémique. La première partie est dédiée à l’étude de processus d’activation chimique important non seulement pour la formation de polymères, mais aussi pour alimenter le système en énergie de manière à le maintenir dans un état éloigné de l’équilibre, un prérequis pour l’auto-organisation. Il a été suggéré que les intermédiaires 5(4H)-oxazolones formés par l’activation de l’extrémité C-terminale des peptides pourrait être impliquée dans l’auto-organisation du vivant. Dans ce but, nous avons évalué la réactivité de réactifs pertinents dans un contexte prébiotique et décrits dans la littérature comme capables d’activer des acides α-aminés. Aucun d’entre eux n’a manifesté une activité satisfaisante pour l’activation C-terminale des peptides, montrant qu’une voie possible pour alimenter un protométabolisme des peptides en énergie n’est pas identifiée à ce jour à l’exception notable des N-carboxyanhydrides (NCA) qui peuvent être formé par des voies prébiotiquement plausibles. Nous avons par ailleurs démontré que les carbodiimides sont aussi efficaces pour l’activation des N-carbamoylamino acides que pour celle du carboxyle terminal des peptides en milieu aqueux dilué. La seconde partie du document expose de nouveaux résultats en faveur d’un processus de coévolution peptides-nucléotides. D’abord, une étude de la réactivité d’agents d’aminoacylation de l’extrémité 3’ de l’ARN est présentée. Ensuite, nous évaluons des co-polymères acides α-aminés-nucléotides liés par des enchaînements phosphoramidate et esters comme partenaires éventuels de l’évolution chimique. La pertinence cinétique de ces structures est démontrée ainsi que des voies chimiques permettant leur formation
The thesis addresses several issues in prebiotic chemistry in the context of the origins of life through a systems chemistry approach. The first part is devoted to the study of chemical activation processes that are not only important in the formation of polymers, but also to feed the system with energy in order that a far from equilibrium state is maintained, a prerequisite for self-organization. It has been suggested that 5(4H)-oxazolones intermediates formed by C-terminus peptide activation could be involved in self-organization of life. To this aim, we have checked the reactivity of relevant prebiotic reagents previously proposed to activate α-amino acids. None of them led to a satisfactory C-terminus activation of peptides, showing that no general process for feeding a protometabolism of peptides with energy is identified yet, with the notable exception of N-carboxyanhydrides (NCAs) that can be formed through prebiotically relevant pathways. Additionally, we demonstrated that carbodiimides reagents are as efficient in the activation of N-carbamoyl amino acids as in that of the C-terminus of peptides in diluted aqueous media. The second part of the dissertation discloses new results in support of a process of coevolution of peptides and nucleotides. Firstly, a study of non-enzymatic aminoacylation reagents of the 3’-terminus of RNA is presented. Secondly, we assessed co-polymers of α-amino acids and nucleotides bound by phosphoramidate and ester linkages as potential players in chemical evolution. The kinetic relevance of these structures was demonstrated as well as potential chemical processes that allow their formation

Un scénario incontournable aux origines de la vie est celui du « monde ARN ». Pour le valider, il est nécessaire d’expliquer comment les premières molécules d’ARN se sont formées à partir de précurseurs moléculaires plus simples. Reste à savoir si les nucléobases non canoniques ont été formées parallèlement aux canoniques ou plus tard, lorsque la vie a nécessité une plus grande diversité fonctionnelle. Notre hypothèse est que les voies métaboliques modernes pourraient être en partie héritées des réseaux de réactions abiotiques, compatibles avec le contexte géochimique. Ces réseaux seraient le résultat d’une série de réactions établies par l’interaction de molécules organiques avec des minéraux inorganiques. Le rôle catalytique aurait alors été joué par une catalyse hétérogène sur des sites de surface. Les réactions thermodynamiquement défavorables pourraient s’appuyer, sur des surfaces minérales et sur d’autres sources d’énergie libre que les molécules d’ATP : molécules inorganiques de haute énergie ou exploitation de déséquilibres macroscopiques. Afin de tester cette hypothèse, la voie de l’orotate, menant à la synthèse de l’uracile, est étudiée ici pour tester comment les voies protométaboliques se sont développées dans un monde prébiotique exempt d’enzymes et comment le contexte géochimique a affecté les origines de la vie. Le carbamyl phosphate (CP) est le premier synthon à haute énergie à intervenir dans la biosynthèse de l’uridine monophosphate. Nous avons donc étudié la probabilité de sa présence dans des conditions prébiotiques. L’évolution du CP dans l’eau et en solution ammoniacale a été caractérisée à l’aide des spectroscopies ATR-IR, RMN 31P et 13C. A l’ambiante, le CP se transforme en cyanate et en carbamate/hydrogénocarbonate en quelques heures. Le cyanate, moins labile que le CP, demeure un potentiel donneur de carbamyle. En présence d’ammoniac, la décomposition du CP est plus rapide, générant urée et amidophosphates. Nous en concluons que le CP en tant que tel n’est pas un réactif prébiotique probable. Le cyanate et l’urée sont des substituts plus prometteurs que le CP car ils sont riches en énergie et cinétiquement inertes face à l’hydrolyse. Des molécules inorganiques riches en énergie (trimétaphosphate, phosphoramidates) ont également été étudiées pour déterminer si elles pouvaient être sources de carbamyl phosphate. Bien que ces espèces n’aient pas produit de CP, elles ont présenté une transduction d’énergie : la formation de liaisons P-N. Dans la cellule, la deuxième étape de la synthèse des monomères pyrimidiques de l’ARN est la carbamylation de l’aspartate. Nous avons comparé la réaction biosynthétique à deux scénarios sans enzyme : en solution aqueuse et sur minéral imprégné. La synthèse abiotique sur minéral du squelette linéaire de pyrimidine (acide N-carbamylaspartique, NCA) a été effectuée sur une plage thermique allant jusqu’à 250 °C. Bien que l’utilisation de différents donneurs de carbamyle soit conditionnée par la thermodynamique, la cinétique joue un rôle déterminant dans le choix des voies possibles pour la carbamylation de l’acide aspartique. Dans la dernière étape, nous avons exploré en détail la cyclisation du NCA. Nous avons procédé à la caractérisation in situ (ATG, IR) et ex situ (RMN 1H) des précurseurs de la pyrimidine après adsorption et activation thermique sur un large éventail de minéraux. Nos données suggèrent un possible carrefour métabolique pour l’origine chimique des bases canoniques et non canoniques. Nous montrons que les équivalents inorganiques peuvent remplacer l’enzyme effectuant cette étape, mais aussi d’autres membres de sa famille enzymatique (amidohydrolases cycliques) effectuant des réactions de cyclisation. Enfin, les résultats préliminaires évaluent le rôle des conditions redox, sur la base de la chimie du fer, afin de mieux comprendre la formation de l’acide orotique, ainsi que le rôle prépondérant des minéraux dans la réaction formose à l’interface gaz/solide
A promising scenario for the origins of life is that of the «RNA world». To validate this model, it is necessary to explain how the first RNA molecules were born out of simpler molecular precursors. An unsolved question is whether noncanonical nucleobases were formed in parallel to the canonical ones or later, when life required higher functional diversity. Our hypothesis is that modern metabolic pathways could be partly inherited from previously existing abiotic reaction networks, provided they respect the geochemical context. These networks would be the result of a series of reactions established by the interaction of organic molecules with inorganic minerals. The catalytic role, entrusted to enzymes in modern biochemistry, would then have been played by heterogeneous catalysis on specific surface sites. The input of free energy to achieve thermodynamically unfavourable steps could rely on the mineral surfaces, on high energy inorganic molecules, or on macroscopic imbalances.To test this hypothesis in a specific case, the orotate pathway which leads to uracil synthesis, is studied here to test how protometabolic paths developed in an enzyme-free prebiotic world and how geochemical context affected the origins of life. Carbamoyl phosphate (CP) is the first high-energy building block that intervenes in the biosynthesis of uridine monophosphate. Thus, we investigated the likelihood of its occurrence in prebiotic conditions. The evolution of carbamoyl phosphate in water and in aqueous ammonia solutions without enzymes was characterised using ATR-IR, 31P and 13C spectroscopies. Carbamoyl phosphate in water at ambient conditions transforms to cyanate and carbamate/hydrogenocarbonate species within a matter of hours. Cyanate, less labile than CP, remains a potential carbamoylating agent. In ammonia solution, CP decomposition occurs more rapidly and generates urea. We conclude that CP is not a likely prebiotic reagent. Cyanate and urea are more promising substitutes for CP, as they are both “energy-rich” (high free enthalpy molecules in aqueous solutions) and kinetically inert toward hydrolysis. Energy-rich inorganic molecules (trimetaphosphate, phosphoramidates) were also explored for their suitability as sources of carbamoyl phosphate. Although these species did not generate carbamoylating agents, they exhibited energy transduction, specifically the formation of high-energy P–N bonds. In the living cell, the second step of synthesizing pyrimidine RNA monomers is a carbamoyl transfer from a carbamoyl donor to aspartic acid. We compared the biosynthetic reaction to two enzyme-free scenarios: aqueous and dried/wetted mineral. Mineral-assisted abiotic synthesis of the pyrimidine linear skeleton (carbamoyl aspartic acid) was performed over a thermal range from 25 °C up to 250 °C. In addition to aqueous synthesis of pyrimidine nucleobases, which is executed at 25 °C for 16 h, the catalytic properties of silica and hydromagnesite minerals were explored. While the use of various carbamoyl donors is enabled by thermodynamics, kinetics plays a determining role in selecting possible paths for the carbamoylation of aspartic acid as a start for building nucleobases. In the last step we explored in detail the cyclization of N-carbamoyl aspartic acid (NCA). We carried out in situ (TGA, IR) and ex situ (1H NMR) characterization of pyrimidine precursors after adsorption and thermal activation on a wide range of minerals. Our data suggest a possible metabolic crossroad for the chemical origin of canonical and noncanonical bases. We show that inorganic equivalents can replace the enzyme carrying out this synthetic step, but also other members of its enzymatic family (cyclic amidohydrolases). Finally, preliminary results evaluate the role of redox conditions, based on iron chemistry to better understand the orotic acid formation from dihydroorotate, as well as the prominent role of minerals in the formose reaction at the gas/solid interface