scholarly journals Prebiotic Synthesis of α-Amino Acids and Orotate from α-Ketoacids Potentiates Transition to Extant Metabolic Pathways

2021 ◽  
Author(s):  
Ramanarayanan Krishnamurthy ◽  
Sunil Pulletikurti ◽  
Mahipal Yadav ◽  
Greg Springsteen
Keyword(s):  
Amino Acids ◽  
Metabolic Pathways ◽  
Prebiotic Chemistry ◽  
Krebs Cycle ◽  
Prebiotic Synthesis ◽  
Biological Pathways ◽  
Subsequent Evolution ◽  
Simultaneous Formation ◽  
Strecker Reaction ◽  
Seamless Transition

Abstract The Strecker reaction of aldehydes is the preeminent pathway to explain the prebiotic origins of a-amino acids. However, biology employs transamination of a-ketoacids to give rise to amino acids which are then transformed to nucleobases, implying subsequent evolution of the biosynthetic pathways – abiotically or biotically. Herein, we show that a-ketoacids react with cyanide and ammonia sources to form the corresponding a-amino acids – via the Bucherer-Bergs pathway. An efficient prebiotic transformation of oxaloacetate to aspartate via N-carbamoyl aspartate enables the simultaneous formation of dihydroorotate, paralleling the biochemical synthesis of orotate as the precursor to pyrimidine nucleobases. Glyoxylate forms both glycine and orotate, and reacts with malonate and urea to form aspartate and dihydroorotate. These results, along with the previously demonstrated protometabolic analogs of the Krebs cycle suggest that there can be a natural emergence of congruent forerunners of biological pathways with the potential for seamless transition from prebiotic chemistry to modern metabolism.

scholarly journals Prebiotic Synthesis of Cysteine Peptides That Catalyze Peptide Ligation in Neutral Water

2020 ◽  
Author(s):  
Callum Foden ◽  
Saidul Islam ◽  
Christian Arturo Fernandez Garcia ◽  
Leonardo Maugeri ◽  
Tom Sheppard ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Chemical Synthesis ◽  
Prebiotic Synthesis ◽  
Biomimetic Synthesis ◽  
Strecker Reaction ◽  
Simple Chemical ◽  
Peptide Biosynthesis ◽  
Neutral Water ◽  
Life On Earth

<div>Peptides and the proteinogenic α-amino acids are essential to all life on Earth. Peptide biosynthesis is orchestrated by a complex suite of enzymes in extant biology, but this must have been predated by a simple chemical synthesis at the origins of life. α-Aminonitriles, the nitrile precursors of α-amino acids, are generally readily produced by Strecker reactions, but the origin of cysteine—the thiol-bearing amino acid—is not understood. The aminothiol moiety of cysteine is chemically incompatible with nitriles at physiological pH, therefore cysteine nitrile is not stable, and it is widely believed that cysteine was a biological invention and a late addition to the genetic code<sub>.</sub> Here, we report the first high-yielding, prebiotic synthesis of cysteine peptides. Our biomimetic synthesis converts serine to cysteine, by-passing the Strecker reaction of β-mercaptoacetaldehyde, but exploits nitrile–activated dehydroalanine synthesis at near-neutral pH. We additionally demonstrate the catalytic prowess of <i>N</i>-acylcysteines (and related peptides and thiols) in the organocatalytic synthesis of peptides and peptidyl amidines in neutral water. Thiol catalysis directly couples kinetically stable—but energy-rich—α-amidonitriles to proteinogenic amines, in a reaction that tolerates all twenty proteinogenic side chains. This is a rare, prebiotically plausible example of selective and efficient organocatalysis in water. Our results implicate cysteine derivatives and thiol-catalysis at the onset of evolution.</div>

scholarly journals An appeal to magic? The discovery of a non-enzymatic metabolism and its role in the origins of life

2018 ◽  
Vol 475 (16) ◽  
pp. 2577-2592 ◽  
Author(s):  
Markus Ralser
Keyword(s):  
Amino Acids ◽  
Metabolic Pathway ◽  
Metal Cation ◽  
Hydrogen Cyanide ◽  
Metabolic Pathways ◽  
Co2 Fixation ◽  
Enzymatic Reaction ◽  
Krebs Cycle ◽  
Pentose Phosphate ◽  
Long Time

Until recently, prebiotic precursors to metabolic pathways were not known. In parallel, chemistry achieved the synthesis of amino acids and nucleotides only in reaction sequences that do not resemble metabolic pathways, and by using condition step changes, incompatible with enzyme evolution. As a consequence, it was frequently assumed that the topological organisation of the metabolic pathway has formed in a Darwinian process. The situation changed with the discovery of a non-enzymatic glycolysis and pentose phosphate pathway. The suite of metabolism-like reactions is promoted by a metal cation, (Fe(II)), abundant in Archean sediment, and requires no condition step changes. Knowledge about metabolism-like reaction topologies has accumulated since, and supports non-enzymatic origins of gluconeogenesis, the S-adenosylmethionine pathway, the Krebs cycle, as well as CO2 fixation. It now feels that it is only a question of time until essential parts of metabolism can be replicated non-enzymatically. Here, I review the ‘accidents’ that led to the discovery of the non-enzymatic glycolysis, and on the example of a chemical network based on hydrogen cyanide, I provide reasoning why metabolism-like non-enzymatic reaction topologies may have been missed for a long time. Finally, I discuss that, on the basis of non-enzymatic metabolism-like networks, one can elaborate stepwise scenarios for the origin of metabolic pathways, a situation that increasingly renders the origins of metabolism a tangible problem.

scholarly journals Prebiotic Synthesis of Cysteine Peptides That Catalyze Peptide Ligation in Neutral Water

2020 ◽  
Author(s):  
Callum Foden ◽  
Saidul Islam ◽  
Christian Arturo Fernandez Garcia ◽  
Leonardo Maugeri ◽  
Tom Sheppard ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Chemical Synthesis ◽  
Prebiotic Synthesis ◽  
Biomimetic Synthesis ◽  
Strecker Reaction ◽  
Simple Chemical ◽  
Peptide Biosynthesis ◽  
Neutral Water ◽  
Life On Earth

<div>Peptides and the proteinogenic α-amino acids are essential to all life on Earth. Peptide biosynthesis is orchestrated by a complex suite of enzymes in extant biology, but this must have been predated by a simple chemical synthesis at the origins of life. α-Aminonitriles, the nitrile precursors of α-amino acids, are generally readily produced by Strecker reactions, but the origin of cysteine—the thiol-bearing amino acid—is not understood. The aminothiol moiety of cysteine is chemically incompatible with nitriles at physiological pH, therefore cysteine nitrile is not stable, and it is widely believed that cysteine was a biological invention and a late addition to the genetic code<sub>.</sub> Here, we report the first high-yielding, prebiotic synthesis of cysteine peptides. Our biomimetic synthesis converts serine to cysteine, by-passing the Strecker reaction of β-mercaptoacetaldehyde, but exploits nitrile–activated dehydroalanine synthesis at near-neutral pH. We additionally demonstrate the catalytic prowess of <i>N</i>-acylcysteines (and related peptides and thiols) in the organocatalytic synthesis of peptides and peptidyl amidines in neutral water. Thiol catalysis directly couples kinetically stable—but energy-rich—α-amidonitriles to proteinogenic amines, in a reaction that tolerates all twenty proteinogenic side chains. This is a rare, prebiotically plausible example of selective and efficient organocatalysis in water. Our results implicate cysteine derivatives and thiol-catalysis at the onset of evolution.</div>

scholarly journals Integrated Synthesis of Nucleotide and Nucleosides Directed by Amino Acids

2018 ◽  
Author(s):  
Irene Suárez-Marina ◽  
Rebecca Turk-MacLeod ◽  
Yousef M. Abul-Haija ◽  
Piotr S. Gromski ◽  
Geoffrey Cooper ◽  
...  
Keyword(s):  
Amino Acids ◽  
Prebiotic Chemistry ◽  
Building Blocks ◽  
Reaction Networks ◽  
One Pot ◽  
Simultaneous Formation ◽  
Chemical Systems ◽  
Mild Conditions ◽  
Glycosidic Bonds ◽  
Selection Of

<p><b>Research on the origin of nucleic acids and proteins has been approached by either multi-step synthesis or simple one-pot reactions, but exploration of their prebiotic chemistry is normally done separately. However, if nucleotides and amino acids co-existed on early Earth, their mutual interactions and reactivity should be considered in exploring the emergence of complex chemical systems that can ultimately evolve. To explore this idea, we set out to investigate nucleotide/nucleoside formation by a simple dehydration reaction of the constituent building blocks (sugar, phosphate, and nucleobase) in the presence of amino acids (<i>i.e.</i> glycine,</b> <b>arginine, glutamic acid, threonine, methionine, phenylalanine and tryptophan). Herein, we report the first example of simultaneous formation of glycosidic bonds between ribose, purines, and pyrimidines under mild conditions without a catalyst or activated reagents, as well as nucleobase exchange. We observed not only the simultaneous formation of nucleotide and nucleoside isomers from several nucleobases, but also the selection of distribution of glycosylation products when glycine was present. This work shows how reaction networks of nucleotides and amino acids should be considered when exploring the emergence of catalytic networks in the context of molecular evolution. </b></p>

scholarly journals Integrated Synthesis of Nucleotide and Nucleosides Directed by Amino Acids

2018 ◽  
Author(s):  
Irene Suárez-Marina ◽  
Rebecca Turk-MacLeod ◽  
Yousef M. Abul-Haija ◽  
Piotr S. Gromski ◽  
Geoffrey Cooper ◽  
...  
Keyword(s):  
Amino Acids ◽  
Prebiotic Chemistry ◽  
Building Blocks ◽  
Reaction Networks ◽  
One Pot ◽  
Simultaneous Formation ◽  
Chemical Systems ◽  
Mild Conditions ◽  
Glycosidic Bonds ◽  
Selection Of

<p><b>Research on the origin of nucleic acids and proteins has been approached by either multi-step synthesis or simple one-pot reactions, but exploration of their prebiotic chemistry is normally done separately. However, if nucleotides and amino acids co-existed on early Earth, their mutual interactions and reactivity should be considered in exploring the emergence of complex chemical systems that can ultimately evolve. To explore this idea, we set out to investigate nucleotide/nucleoside formation by a simple dehydration reaction of the constituent building blocks (sugar, phosphate, and nucleobase) in the presence of amino acids (<i>i.e.</i> glycine,</b> <b>arginine, glutamic acid, threonine, methionine, phenylalanine and tryptophan). Herein, we report the first example of simultaneous formation of glycosidic bonds between ribose, purines, and pyrimidines under mild conditions without a catalyst or activated reagents, as well as nucleobase exchange. We observed not only the simultaneous formation of nucleotide and nucleoside isomers from several nucleobases, but also the selection of distribution of glycosylation products when glycine was present. This work shows how reaction networks of nucleotides and amino acids should be considered when exploring the emergence of catalytic networks in the context of molecular evolution. </b></p>

Sulfur amino acids: from prebiotic chemistry to biology and vice versa

Synthesis ◽  
2021 ◽  
Author(s):  
Sparta Youssef-Saliba ◽  
Yannick Vallée
Keyword(s):  
Amino Acids ◽  
Essential Role ◽  
Prebiotic Chemistry ◽  
Prebiotic Synthesis ◽  
Sulfur Amino Acids ◽  
Methionine Residue ◽  
Catalytic Sites ◽  
Protein Amino Acids ◽  
Sulfur Containing

Two sulfur containing amino acids are included in the list of the 20 classical protein amino acids. A methionine residue is introduced at the start of the synthesis of all current proteins. Cysteine, thanks to its thiol function, plays an essential role in a very large number of catalytic sites. Here we present what is known about the prebiotic synthesis of these two amino acids and homocysteine, and we discuss their introduction into primitive peptides and more elaborate proteins.

Synthesis and Breakdown of the Universal Precursors to Biological Metabolism Promoted by Ferrous Iron

2018 ◽  
Author(s):  
Kamila B. Muchowska ◽  
Sreejith Jayasree VARMA ◽  
Joseph Moran
Keyword(s):  
Amino Acids ◽  
Chemical Reaction ◽  
Metabolic Pathways ◽  
Ferrous Iron ◽  
Reaction Network ◽  
Tca Cycle ◽  
Chemical Reaction Network ◽  
Metabolic Precursors ◽  
Tca Cycle Intermediates

How core biological metabolism initiated and why it uses the intermediates, reactions and pathways that it does remains unclear. Life builds its molecules from CO<sub>2 </sub>and breaks them down to CO<sub>2 </sub>again through the intermediacy of just five metabolites that act as the hubs of biochemistry. Here, we describe a purely chemical reaction network promoted by Fe<sup>2+ </sup>in which aqueous pyruvate and glyoxylate, two products of abiotic CO<sub>2 </sub>reduction, build up nine of the eleven TCA cycle intermediates, including all five universal metabolic precursors. The intermediates simultaneously break down to CO<sub>2 </sub>in a life-like regime resembling biological anabolism and catabolism. Introduction of hydroxylamine and Fe<sup>0 </sup>produces four biological amino acids. The network significantly overlaps the TCA/rTCA and glyoxylate cycles and may represent a prebiotic precursor to these core metabolic pathways.

scholarly journals Prebiotic synthesis of aminooxazoline-5′-phosphates in water by oxidative phosphorylation

2017 ◽  
Vol 53 (36) ◽  
pp. 4919-4921 ◽  
Author(s):  
C. Fernández-García ◽  
N. M. Grefenstette ◽  
M. W. Powner
Keyword(s):  
Amino Acids ◽  
Oxidative Phosphorylation ◽  
Prebiotic Synthesis ◽  
Strecker Synthesis ◽  
Novel Strategy

A novel strategy for aminooxazoline-5′-phosphate synthesis in water from prebiotic feedstocks, which is generationally linked to Strecker synthesis of proteinogenic amino acids.

scholarly journals Formaldehyde and De/Methylation in Age-Related Cognitive Impairment

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 913
Author(s):  
Ting Li ◽  
Yan Wei ◽  
Meihua Qu ◽  
Lixian Mou ◽  
Junye Miao ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cell Proliferation ◽  
Cognitive Impairment ◽  
Metabolic Pathways ◽  
Memory Formation ◽  
Epigenetic Alterations ◽  
Diagnostic Biomarker ◽  
Reactive Substance ◽  
Age Related ◽  
Novel Therapeutic

Formaldehyde (FA) is a highly reactive substance that is ubiquitous in the environment and is usually considered as a pollutant. In the human body, FA is a product of various metabolic pathways and participates in one-carbon cycle, which provides carbon for the synthesis and modification of bio-compounds, such as DNA, RNA, and amino acids. Endogenous FA plays a role in epigenetic regulation, especially in the methylation and demethylation of DNA, histones, and RNA. Recently, epigenetic alterations associated with FA dysmetabolism have been considered as one of the important features in age-related cognitive impairment (ARCI), suggesting the potential of using FA as a diagnostic biomarker of ARCI. Notably, FA plays multifaceted roles, and, at certain concentrations, it promotes cell proliferation, enhances memory formation, and elongates life span, effects that could also be involved in the aetiology of ARCI. Further investigation of and the regulation of the epigenetics landscape may provide new insights about the aetiology of ARCI and provide novel therapeutic targets.

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