From Amino Acids to α‐Keto Acids via β‐Elimination and Transamination Initiates a Pathway to Prebiotic Reaction Networks

α-Keto acids, such as pyruvate and glyoxylate, may have been critical in generating reaction networks at the origins of life due to their facile carbon-carbon bond formation and their hydrolytic stability. However, demonstrated prebiotic sources of these small α-keto acids have been limited by conditions required for their production, which are not conducive for subsequent incorporation or transition into (proto)metabolic pathways. Here, we demonstrate an abiotic generation of α-keto acids from only two amino acids, starting with the phosphorylation and dehydration of serine (Ser) coupled with a transamination with glycine (Gly), to produce both pyruvate and glyoxylate. This triggers an in situ reaction pathway producing higher-order α-keto acids, including amino acid precursors found in modern biology. These findings may help elucidate how protometabolic chemical networks can emerge on the early Earth under mild aqueous conditions, leading to a coupled amino acid-α-keto acid chemical system capable of supporting a more robust metabolism.

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Publication Details

Journal
Angewandte Chemie International Edition
Published
2025-05-09
DOI
https://doi.org/10.1002/anie.202507248
Citations
1
Primary Topic
Origins and Evolution of Life
Type
article
Field-Weighted Citation Impact
1.15

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article

From Amino Acids to α‐Keto Acids via β‐Elimination and Transamination Initiates a Pathway to Prebiotic Reaction Networks

Kevin Ryan, R. Trent Stubbs, Ramanarayanan Krishnamurthy, Greg Springsteen et al.
1 citations
Angewandte Chemie International Edition
Origins and Evolution of Life
1.15
article

From Amino Acids to α‐Keto Acids via β‐Elimination and Transamination Initiates a Pathway to Prebiotic Reaction Networks

Kevin Ryan, R. Trent Stubbs, Ramanarayanan Krishnamurthy, Greg Springsteen, Louis M. P. Ter‐Ovanessian, Joshua Shaarda
article en
1 citations

Abstract

α-Keto acids, such as pyruvate and glyoxylate, may have been critical in generating reaction networks at the origins of life due to their facile carbon-carbon bond formation and their hydrolytic stability. However, demonstrated prebiotic sources of these small α-keto acids have been limited by conditions required for their production, which are not conducive for subsequent incorporation or transition into (proto)metabolic pathways. Here, we demonstrate an abiotic generation of α-keto acids from only two amino acids, starting with the phosphorylation and dehydration of serine (Ser) coupled with a transamination with glycine (Gly), to produce both pyruvate and glyoxylate. This triggers an in situ reaction pathway producing higher-order α-keto acids, including amino acid precursors found in modern biology. These findings may help elucidate how protometabolic chemical networks can emerge on the early Earth under mild aqueous conditions, leading to a coupled amino acid-α-keto acid chemical system capable of supporting a more robust metabolism.

Angewandte Chemie International EditionVol. 64(29)
Scripps Research Institute (US), Furman University (US)
National Science Foundation, National Aeronautics and Space Administration, Nuclear Safety and Security Commission
Openalex Percentile: Top 19%
Origins and Evolution of Life
1.15
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From Amino Acids to α‐Keto Acids via β‐Elimination and Transamination Initiates a Pathway to Prebiotic Reaction Networks — Kevin Ryan, R. Trent Stubbs, et al. · Angewandte Chemie International Edition (2025) | TGRS Research Map | TGRS