Cysteine <i>S</i> ‐conjugate sulfoxide β‐lyase activity for human <scp>ACCS</scp>

1-Aminocyclopropane-1-carboxylate synthase (ACCS) catalyzes the conversion of S-adenosyl-methionine to 1-aminocyclopropane-1-carboxylate (ACC), a rate-limiting step in ethylene biosynthesis. A gene encoding a putative ACCS protein was identified in the human genome two decades ago. It has been shown to not exhibit any canonical ACC synthase activity and its true function remains obscure. In this study, through a biochemical profiling approach, we demonstrate that human ACCS possesses cysteine conjugate sulfoxide β-lyase activity. This function is unexpected but reasonable, as it somewhat parallels the activity of ACCS proteins found in non-seed plants. Structure-function relationship study of human ACCS, guided by an AlphaFold2 model, allowed us to identify key active site residues that are important for its β-lyase activity. Our biochemical study of human ACCS also provided insights into the function of other mammalian ACCS homologs.