Forged in O₂: Transition metal ions and the rise of aerobic life

The evolution of oxidative metabolism has shaped life on Earth, from ancient anaerobic microorganisms to modern eukaryotes. Central to aerobic life is the ability of metalloproteins to regulate and utilize dioxygen through tightly controlled biochemical processes. Beginning with the emergence of oxygenic photosynthesis and aerobic respiration, the pivotal roles of metalloenzymes in dioxygen activation, utilization and detoxification are then highlighted. Bridging perspectives from bioinorganic chemistry, enzymology, synthetic biology and microbiome science, we discuss how studies of biomimetic molecular complexes and natural and artificial metalloproteins illuminate the structural and functional strategies used to manage dioxygen reactivity. We further consider the systemic roles of metal ions in maintaining redox balance, shaping host-microbe interactions, and contributing to pathological outcomes when misregulated. A foundation is established for understanding the critical roles that metal ions play in dioxygen chemistry that underpins both healthy metabolism and oxidative stress related diseases.