Birth of a pathway for sulfur metabolism in early amniote evolution

Among amniotes, reptiles and mammals are differently adapted to terrestrial life. It is well appreciated that terrestrialization required adaptive changes of vertebrate metabolism, particularly in the mode of nitrogen excretion. However, the current paradigm is that metabolic adaptation to life on land did not involve synthesis of enzymatic pathways de novo but repurposing of existing ones. Here, by comparing the inventory of pyridoxal phosphate-dependent enzymes (PLPome) in different amniotes, we identify in silico a pathway for sulfur metabolism present in chick embryos and other reptiles but not in mammals. Cysteine lyase (CL) contains heme and PLP cofactors and converts cysteine and sulfite into cysteic acid and hydrogen sulfide. A specific cysteic acid decarboxylase (CAD) produces taurine while hydrogen sulfide is recycled into cysteine by cystathionine beta-synthase (CBS). This reaction sequence enables the formation of sulfonated amino acids during embryo development in the egg at no cost of reduced sulfur. The pathway originated around 300 million years ago in a proto-reptile by CBS duplication, CL neofunctionalization, and CAD co-option. Our findings indicate that adaptation to terrestrial life involved innovations in metabolic pathways and reveal the molecular mechanisms by which such innovations arose in amniote evolution.