Journal Article

A plausible metal-free ancestral analogue of the Krebs cycle composed entirely of α-ketoacids

Springsteen, Greg, Krishnamurthy Ramanarayanan, Trent, Stubbs R, Yadav Mahipal

2020

Overview

Efforts to decipher the prebiotic roots of metabolic pathways have focused on recapitulating modern biological transformations, with metals typically serving in place of cofactors and enzymes. Here we show that the reaction of glyoxylate with pyruvate under mild aqueous conditions produces a series of α-ketoacid analogues of the reductive citric acid cycle without the need for metals or enzyme catalysts. The transformations proceed in the same sequence as the reverse Krebs cycle, resembling a protometabolic pathway, with glyoxylate acting as both the carbon source and reducing agent. Furthermore, the α-ketoacid analogues provide a natural route for the synthesis of amino acids by transamination with glycine, paralleling the extant metabolic mechanisms and obviating the need for metal-catalysed abiotic reductive aminations. This emerging sequence of prebiotic reactions could have set the stage for the advent of increasingly sophisticated pathways operating under catalytic control.Metal-catalysed prebiotic reactions have been proposed as forerunners of modern metabolism. Now, an abiotic pathway resembling the reverse tricarboxylic acid cycle has been shown to proceed without metal catalysis. The reaction of glyoxylate and pyruvate produces a series of α-ketoacid tricarboxylic acid analogues, and provides a route to generate α-amino acids by transamination.

• Publisher: Nature Publishing Group
• Subject: Amino acids / Carbon sources / Catalysis / Catalysts / Citric acid / Cofactors / Glycine / Krebs cycle / Metabolic pathways / Metabolism / Metals / Prebiotics / Pyruvic acid / Reducing agents / Tricarboxylic acid cycle