Sulfate radicals enable a non-enzymatic Krebs cycle precursor

Area of Science:

• Biochemistry
• Astrobiology
• Geochemistry

Background:

• The evolutionary origins of the tricarboxylic acid cycle (TCA), or Krebs cycle, remain unclear.
• Previous dismissal of non-enzymatic Krebs cycle catalysts has been challenged by the discovery of intermediates on meteorites and their non-enzymatic interconversion.

Purpose of the Study:

• To identify a non-enzymatic catalyst for the Krebs cycle.
• To investigate the potential for spontaneous formation of TCA cycle precursors in early Earth conditions.

Main Methods:

• Utilized combinatorial, quantitative high-throughput metabolomics.
• Systematically screened iron and sulfate reaction environments mimicking Archean sediment constituents.

Main Results:

• TCA cycle intermediates are stable in water and most iron/sulfate species.
• Identified 24 non-enzymatic interconversion reactions of TCA intermediates mediated by sulfate radicals (from peroxydisulfate).
• These reactions replicate the topology of the Krebs cycle, glyoxylate shunt, and succinic semialdehyde pathways with over 90% carbon recovery.

Conclusions:

• A non-enzymatic precursor for the Krebs cycle is biologically plausible and efficient.
• These reactions can form spontaneously under conditions involving sulfate radicals, suggesting a potential prebiotic pathway.