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

Science ◽  
2020 ◽  
Vol 370 (6518) ◽  
pp. 865-869 ◽  
Author(s):  
Callum S. Foden ◽  
Saidul Islam ◽  
Christian Fernández-García ◽  
Leonardo Maugeri ◽  
Tom D. Sheppard ◽  
...  
Keyword(s):  
Amino Acid ◽  
Chemical Synthesis ◽  
Prebiotic Chemistry ◽  
Prebiotic Synthesis ◽  
Simple Chemical ◽  
Peptide Biosynthesis ◽  
Prebiotic Peptide Synthesis ◽  
Neutral Water ◽  
Amino Acid Precursors ◽  
Peptide Ligation

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.

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 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 Arcopilus aureus MaC7A as a New Source of Resveratrol: Assessment of Amino Acid Precursors, Volatiles, and Fungal Enzymes for Boosting Resveratrol Production in Batch Cultures

2021 ◽  
Vol 11 (10) ◽  
pp. 4583
Author(s):  
Nemesio Villa-Ruano ◽  
Luis Ángel Morales-Mora ◽  
Jenaro Leocadio Varela-Caselis ◽  
Antonio Rivera ◽  
María de los Ángeles Valencia de Ita ◽  
...  
Keyword(s):  
Amino Acid ◽  
Filamentous Fungi ◽  
Hydrolytic Enzymes ◽  
Glucanase Activity ◽  
Fungal Enzymes ◽  
Activity Increase ◽  
Batch Cultures ◽  
Low Concentrations ◽  
Chemical Factors ◽  
Amino Acid Precursors

The chemical factors that regulate the synthesis of resveratrol (RV) in filamentous fungi are still unknown. This work reports on the RV production by Arcopilus aureus MaC7A under controlled conditions and the effect of amino acid precursors (PHE and TYR), monoterpenes (limonone, camphor, citral, thymol, menthol), and mixtures of hydrolytic enzymes (Glucanex) as elicitors for boosting fungal RV. Batch cultures with variable concentrations of PHE and TYR (50–500 mg L−1) stimulated RV production from 127.9 ± 4.6 to 221.8 ± 5.2 mg L−1 in basic cultures developed in PDB (pH 7) added with 10 g L−1 peptone at 30 °C. Maximum levels of RV and biomass were maintained during days 6–8 under these conditions, whereas a dramatic RV decrease was observed from days 10–12 without any loss of biomass. Among the tested volatiles, citral (50 mg L−1) enhanced RV production until 187.8 ± 2.2 mg L−1 in basic cultures, but better results were obtained with Glucanex (100 mg L−1; 198.3 ± 7.6 mg L−1 RV). Optimized batch cultures containing TYR (200 mg L−1), citral (50 mg L−1), thymol (50 mg L−1), and Glucanex (100 mg L−1) produced up to 237.6 ± 4.7 mg L−1 of RV. Our results suggest that low concentrations of volatiles and mixtures of isoenzymes with β-1, 3 glucanase activity increase the biosynthesis of fungal RV produced by A. aureus MaC7A in batch cultures.

scholarly journals Chemical Synthesis ofO-Ethyl-L-homoserine, a New Amino Acid Produced byCorynebacterium Ethanolaminophilum

1968 ◽  
Vol 41 (3) ◽  
pp. 633-635 ◽  
Author(s):  
Yoshikatsu Murooka ◽  
Tokuya Harada ◽  
Yoshiharu Izumi
Keyword(s):  
Amino Acid ◽  
Chemical Synthesis

Recyclable BINOL–quinine–squaramide as a highly efficient organocatalyst for α-amination of 1,3-dicarbonyl compounds and α-cyanoacetates

RSC Advances ◽  
2015 ◽  
Vol 5 (31) ◽  
pp. 24392-24398 ◽  
Author(s):  
Yongzhi Gao ◽  
Bin Liu ◽  
Hai-Bing Zhou ◽  
Wei Wang ◽  
Chune Dong
Keyword(s):  
Amino Acid ◽  
Dicarbonyl Compounds ◽  
Highly Efficient ◽  
Amino Acid Precursors

An efficient organocatalytic asymmetric α-amination of 1,3-dicarbonyl and α-cyanoacetates compounds towards chiral α-amino acid precursors is reported.

Sceletium alkaloids. IV. Biosynthesis of mesembrine and related alkaloids. Amino acid precursors

1971 ◽  
Vol 93 (15) ◽  
pp. 3752-3758 ◽  
Author(s):  
P. W. Jeffs ◽  
W. C. Archie ◽  
Richard L. Hawks ◽  
D. S. Farrier
Keyword(s):  
Amino Acid ◽  
Amino Acid Precursors
Sign in / Sign up

Export Citation Format

Share Document