Cysteine Chemistry in Connection with Abiogenesis

Shalayel, Ibrahim; Youssef-Saliba, Sparta; Vazart, Fanny; Ceccarelli, Cecillia; Bridoux, Maxime C.; Vallée, Yannick

doi:10.1002/ejoc.202000089

Cited by 16 publications

(21 citation statements)

References 40 publications

(32 reference statements)

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“…is both an b-aminothiol and an a-aminonitrile it is inherently unstable (7). These observations suggested to us that whilst the Strecker reaction of GCA could yield serine (Ser) under prebiotic conditions, the Strecker reaction of BMA would not play a role in prebiotic Cys synthesis.…”

mentioning

confidence: 91%

“…However, although Strecker reactions are generally highly efficient (23,24), BMA forms intractable and insoluble mixtures in Strecker reactions ( fig. S1) (7). This is in stark contrast to GCA, which undergoes the Strecker reaction in excellent yield to afford a stable aminonitrile product, Ser-CN ( fig.…”

mentioning

confidence: 92%

“…It therefore seems almost inconceivable that cysteinyl thiols were not present during the development of nascent biological processes on the early Earth, and yet this is not the prevailing view (15)(16)(17)(18). Numerous, unsuccessful attempts to synthesize and isolate cysteines under prebiotically plausible conditions (7,(19)(20)(21) have led to a widely-held belief that cysteine is a biological invention (17,18), as well as a late addition to the genetic code (15)(16)(17)(18). Here, we report a high-yielding prebiotic synthesis of cysteines and demonstrate that these cysteine peptides catalyze non-enzymatic CPL in neutral water.…”

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confidence: 99%

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Prebiotic synthesis of cysteine peptides that catalyze peptide ligation in neutral water

Foden

Islam

Fernández-García

et al. 2020

Science

127

118

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Peptide biosynthesis is performed by ribosomes and several other classes of enzymes, but a simple chemical synthesis may have created the first peptides at the origins of life. α-Aminonitriles—prebiotic α–amino acid precursors—are generally produced by Strecker reactions. However, cysteine’s aminothiol is incompatible with nitriles. Consequently, cysteine nitrile is not stable, and cysteine has been proposed to be a product of evolution, not prebiotic chemistry. We now report a high-yielding, prebiotic synthesis of cysteine peptides. Our biomimetic pathway converts serine to cysteine by nitrile-activated dehydroalanine synthesis. We also demonstrate that N-acylcysteines catalyze peptide ligation, directly coupling kinetically stable—but energy-rich—α-amidonitriles to proteinogenic amines. This rare example of selective and efficient organocatalysis in water implicates cysteine as both catalyst and precursor in prebiotic peptide synthesis.

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confidence: 91%

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confidence: 92%

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confidence: 99%

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Prebiotic synthesis of cysteine peptides that catalyze peptide ligation in neutral water

Foden

Islam

Fernández-García

et al. 2020

Science

127

118

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“…However, although Strecker reactions are generally highly efficient 23,24 , BMA forms intractable and insoluble mixtures in Strecker reactions (fig. S1) 7 . This is in stark contrast to GCA, which undergoes the Strecker reaction in excellent yield to afford a stable aminonitrile product, serine nitrile Ser-CN ( fig.…”

Section: Biomimetic Prebiotic Cysteine Synthesismentioning

confidence: 99%

“…S2) 23,24 . The observed disparity between congeners GCA and BMA is likely due to the rapid reaction of b-aminothiols with nitriles in water 25 , and because cysteine nitrile (Cys-CN) is both an b-aminothiol and an a-aminonitrile it is inherently unstable 7 . These observations suggested to us that whilst the Strecker reaction of GCA could yield serine (Ser) under prebiotic conditions, the Strecker reaction of BMA could not play a role in prebiotic Cys synthesis.…”

Section: Biomimetic Prebiotic Cysteine Synthesismentioning

confidence: 99%

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

Foden¹,

Islam²,

Garcia³

et al. 2020

Preprint

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<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>

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Evolutionary Aspects of the Oxido-Reductive Network of Methylglyoxal

Kalapos¹

2021

J Mol Evol

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Cysteine Chemistry in Connection with Abiogenesis

Abstract: Theoretical and experimental work has been conducted about possible prebiotic syntheses of cysteine. Acti-

Cited by 16 publications

References 40 publications

Prebiotic synthesis of cysteine peptides that catalyze peptide ligation in neutral water

Prebiotic synthesis of cysteine peptides that catalyze peptide ligation in neutral water

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

Evolutionary Aspects of the Oxido-Reductive Network of Methylglyoxal

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