A cyanosulfidic origin of the Krebs cycle.

Dougal J. Ritson

doi:10.1126/sciadv.abh3981

Abstract

The centrality of the Krebs cycle in metabolism has long been interpreted as evidence of its antiquity, and consequently, questions regarding its provenance, and whether it initially functioned as a cycle or not, have received much attention. The present report shows that prebiotic oxidation of α-hydroxy carboxylates can be achieved by UV photolysis of a simple geochemical species (HS-), which leads to α-oxo carboxylates that feature in the Krebs cycle and glyoxylate shunt. Further reaction of these products leads to almost all intermediates of the Krebs cycle proper, succinate semialdehyde bypass, and glyoxylate shunt. Fumarate, the missing Krebs cycle component, and the required α-hydroxy carboxylates can be provided by a highly related hydrogen cyanide chemistry, which also provides precursors for amino acids, nucleotides, and phospholipids.

Highlights

The metabolic subsystem of cells links, provisions, and powers the other three cellular subsystems, which in turn, encode, catalyze, and encapsulate it, and the way in which this complex synergistic ensemble arose at the dawn of life is a major enduring enigma
A few years ago, a potentially prebiotic and common origin of nucleotides, amino acids, and lipid precursors was reported, which relied upon the photochemical reduction of hydrogen cyanide using hydrosulfide (HS−) as the stoichiometric reductant [1, 2], thereby challenging traditionally held views that one cellular subsystem must have arisen before all others [3,4,5]
Core components of metabolism were largely absent, and would presumably be required at the onset of biology to replenish the depleted stocks of life’s foundational molecules, e.g., amino acids consumed during oligopeptidesynthesis, consequentially developingbiosynthetic pathways in the process

Summary

Introduction

The metabolic subsystem of cells links, provisions, and powers the other three cellular subsystems, which in turn, encode, catalyze, and encapsulate it, and the way in which this complex synergistic ensemble arose at the dawn of life is a major enduring enigma. The cyanosulfidic network was reevaluated to see whether missing constituents or links to the metabolic subsystem could be found with the added constraint that the chemistry should be compatible with that used to form the other three cellular subsystems [2]. In the reported cyanosulfidic network [2], 12 amino acids are accessed via Strecker synthesis, a reaction that proceeds through an amino acid’s corresponding amino nitrile [6]. The final hydrolysis products of cyanohydrins are the corresponding -hydroxy carboxylates, and a means of oxidizing -hydroxy carboxylates to -oxo carboxylates would provide the penultimate compounds featured in numerous amino acid biosyntheses and suggest a link to extant metabolic pathways. The most recent endeavors to unravel the foundation of the Krebs cycle have focused on reaction networks created from aldol chemistry of 2 and 12, and an oxidative

Methods

Results

Conclusion