Prebiotically plausible chemoselective pantetheine synthesis in water

Jasper  Fairchild; Saidul Islam; Jyoti Singh; Dejan-Krešimir Bučar; Matthew W. Powner

doi:10.1126/science.adk4432

Prebiotically plausible chemoselective pantetheine synthesis in water

Jasper Fairchild, Saidul Islam, Jyoti Singh, Dejan-Krešimir Bučar, Matthew W. Powner

Chemistry

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

86 Downloads (Pure)

Abstract

Coenzyme A (CoA) is essential to all life on Earth, and its functional subunit, pantetheine, is important in many origin-of-life scenarios, but how pantetheine emerged on the early Earth remains a mystery. Earlier attempts to selectively synthesize pantetheine failed, leading to suggestions that “simpler” thiols must have preceded pantetheine at the origin of life. In this work, we report high-yielding and selective prebiotic syntheses of pantetheine in water. Chemoselective multicomponent aldol, iminolactone, and aminonitrile reactions delivered spontaneous differentiation of pantoic acid and proteinogenic amino acid syntheses, as well as the dihydroxyl, gem-dimethyl, and b-alanine-amide moieties of pantetheine in dilute water. Our results are consistent with a role for canonical pantetheine at the outset of life on Earth.

Original language	English
Pages (from-to)	911-918
Number of pages	8
Journal	Science
Volume	383
Issue number	6685
Early online date	22 Feb 2024
DOIs	https://doi.org/10.1126/science.adk4432
Publication status	Published - 23 Feb 2024

Keywords

Chemistry
Prebiotic chemistry
Origin of life
Metabolism
Pantetheine
Coenzyme A
ALDOL REACTIONS
Amide bond
Nitrile
Aminonitrile
Cyanide
Protometabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1126/science.adk4432

Prebiotically plausible chemoselective_FAIRCHILD_2024_GREEN AAMAccepted author manuscript, 1.37 MBLicence: CC BY

Cite this

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title = "Prebiotically plausible chemoselective pantetheine synthesis in water",

abstract = "Coenzyme A (CoA) is essential to all life on Earth, and its functional subunit, pantetheine, is important in many origin-of-life scenarios, but how pantetheine emerged on the early Earth remains a mystery. Earlier attempts to selectively synthesize pantetheine failed, leading to suggestions that “simpler” thiols must have preceded pantetheine at the origin of life. In this work, we report high-yielding and selective prebiotic syntheses of pantetheine in water. Chemoselective multicomponent aldol, iminolactone, and aminonitrile reactions delivered spontaneous differentiation of pantoic acid and proteinogenic amino acid syntheses, as well as the dihydroxyl, gem-dimethyl, and b-alanine-amide moieties of pantetheine in dilute water. Our results are consistent with a role for canonical pantetheine at the outset of life on Earth.",

keywords = "Chemistry, Prebiotic chemistry, Origin of life, Metabolism, Pantetheine, Coenzyme A, ALDOL REACTIONS, Amide bond, Nitrile, Aminonitrile, Cyanide, Protometabolism",

author = "Jasper Fairchild and Saidul Islam and Jyoti Singh and Dejan-Kre{\v s}imir Bu{\v c}ar and Powner, {Matthew W.}",

note = "Funding Information: We thank K. Karu (UCL, mass spectrometry) and A. E. Aliev (UCL, NMR spectroscopy). Funding: This work was supported by the Engineering and Physical Sciences Research Council grants EP/X011755/1 and EP/P020410/1 (M.W.P.), the Simons Foundation grants 318881 and 1154101 (M.W.P.), the Volkswagen Foundation grant 94743 (M.W.P.), and King{\textquoteright}s College London (SI). Publisher Copyright: {\textcopyright} 2024 American Association for the Advancement of Science. All rights reserved.",

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AU - Islam, Saidul

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AU - Powner, Matthew W.

N1 - Funding Information: We thank K. Karu (UCL, mass spectrometry) and A. E. Aliev (UCL, NMR spectroscopy). Funding: This work was supported by the Engineering and Physical Sciences Research Council grants EP/X011755/1 and EP/P020410/1 (M.W.P.), the Simons Foundation grants 318881 and 1154101 (M.W.P.), the Volkswagen Foundation grant 94743 (M.W.P.), and King’s College London (SI). Publisher Copyright: © 2024 American Association for the Advancement of Science. All rights reserved.

PY - 2024/2/23

Y1 - 2024/2/23

N2 - Coenzyme A (CoA) is essential to all life on Earth, and its functional subunit, pantetheine, is important in many origin-of-life scenarios, but how pantetheine emerged on the early Earth remains a mystery. Earlier attempts to selectively synthesize pantetheine failed, leading to suggestions that “simpler” thiols must have preceded pantetheine at the origin of life. In this work, we report high-yielding and selective prebiotic syntheses of pantetheine in water. Chemoselective multicomponent aldol, iminolactone, and aminonitrile reactions delivered spontaneous differentiation of pantoic acid and proteinogenic amino acid syntheses, as well as the dihydroxyl, gem-dimethyl, and b-alanine-amide moieties of pantetheine in dilute water. Our results are consistent with a role for canonical pantetheine at the outset of life on Earth.

AB - Coenzyme A (CoA) is essential to all life on Earth, and its functional subunit, pantetheine, is important in many origin-of-life scenarios, but how pantetheine emerged on the early Earth remains a mystery. Earlier attempts to selectively synthesize pantetheine failed, leading to suggestions that “simpler” thiols must have preceded pantetheine at the origin of life. In this work, we report high-yielding and selective prebiotic syntheses of pantetheine in water. Chemoselective multicomponent aldol, iminolactone, and aminonitrile reactions delivered spontaneous differentiation of pantoic acid and proteinogenic amino acid syntheses, as well as the dihydroxyl, gem-dimethyl, and b-alanine-amide moieties of pantetheine in dilute water. Our results are consistent with a role for canonical pantetheine at the outset of life on Earth.

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KW - Origin of life

KW - Metabolism

KW - Pantetheine

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KW - Amide bond

KW - Nitrile

KW - Aminonitrile

KW - Cyanide

KW - Protometabolism

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Prebiotically plausible chemoselective pantetheine synthesis in water

Abstract

Keywords

UN SDGs

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Cyanide at the origin of metabolism

Prebiotic Catalytic Peptide Ligation Yields Proteinogenic Peptides by Intramolecular Amide Catalyzed Hydrolysis Facilitating Regioselective Lysine Ligation in Neutral Water

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

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