The radical impact of oxygen on prokaryotic evolution—enzyme inhibition first, uninhibited essential biosyntheses second, aerobic respiration third

Abstract

Molecular oxygen is a stable diradical. All O2-dependent enzymes employ a radical mechanism. Generated by cyanobacteria, O2 started accumulating on Earth 2.4 billion years ago. Its evolutionary impact is traditionally sought in respiration and energy yield. We mapped 365 O2-dependent enzymatic reactions of prokaryotes to phylogenies for the corresponding 792 protein families. The main physiological adaptations imparted by O2-dependent enzymes were not energy conservation, but novel organic substrate oxidations and O2-dependent, hence O2-tolerant, alternative pathways for O2-inhibited reactions. Oxygen-dependent enzymes evolved in ancestrally anaerobic pathways for essential cofactor biosynthesis including NAD+, pyridoxal, thiamine, ubiquinone, cobalamin, heme, and chlorophyll. These innovations allowed prokaryotes to synthesize essential cofactors in O2-containing environments, a prerequisite for the later emergence of aerobic respiratory chains.