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Updated: Jun 25, 2025

Metabolic Pathway Confirmation and Discovery Through 13C-labeling of Proteinogenic Amino Acids
Published on: January 26, 2012
A prebiotic Krebs cycle analog generates amino acids with H2 and NH3 over nickel
Harpreet Kaur1, Sophia A Rauscher1, Emilie Werner1
1Institut de Science et d'Ingénierie Supramoléculaires (ISIS), CNRS UMR 7006, Université de Strasbourg, 8 alleé Gaspard Monge, 67000 Strasbourg, France.
Abstract:
Hydrogen (H2) has powered microbial metabolism for roughly 4 billion years. The recent discovery that it also fuels geochemical analogs of the most ancient biological carbon fixation pathway sheds light on the origin of metabolism. However, it remains unclear whether H2 can sustain more complex nonenzymatic reaction networks. Here, we show that H2 drives the nonenzymatic reductive amination of six biological ketoacids and glyoxylate to give the corresponding amino acids in good yields using ammonium concentrations ranging from 6 to 150 mM. Catalytic amounts of nickel or ground meteorites enable these reactions at 22°C and pH 8. The same conditions promote an H2-dependent ketoacid-forming reductive aldol chemistry that co-occurs with reductive amination, producing a continuous reaction network resembling amino acid synthesis in the metabolic core of ancient microbes. The results support the hypothesis that the earliest biochemical networks could have emerged without enzymes or RNA.
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