Darwinian Repurposing of Molecular Motifs in an Evolving Redox Environment and Its Biomedical Implications

The evolution of self-replicating biological species required the prebiotic evolution of fundamental chemical compounds that facilitate critical redox reactions, including chiefly the oxidation of water, the reduction of molecular oxygen, and redox transitions of partially reduced forms of oxygen (reactive oxygen species). The fundamental catalysts for these reactions are porphyrins. Chemically versatile, photoreactive, and redox-active, porphyrins (or their primary precursor, porphin) are believed to have evolved prebiotically in an enthalpically feasible series of reactions. Found throughout biological kingdoms, porphyrins were incorporated in apoproteins in biological evolution and adapted to the specific redox needs of the organisms in which they were active, including photosynthesis, reactive oxygen species metabolism, and oxidative phosphorylation. They did so by virtue of differing transition metal chelates and tetrapyrrole side chains. This article reviews the prebiotic and biotic evolution of porphyrins and porphyrin-bearing apoproteins and suggests that porphyrins' history in evolution reflects a repurposing of molecular motifs as an efficient mechanism for adaptation to a changing redox environment.