Abstract
Acireductone dioxygenase (ARD) is a metalloenzyme of the cupin superfamily, originally isolated from the bacterium Klebsiella oxytoca. ARD catalyzes the oxidative cleavage of the pentultimate intermediate in the methionine salvage pathway, 5‐thiomethyl‐3‐oxo‐1,2‐dihydroxypent‐1‐ene (acireductone) by dioxygen. The products of this oxidation depend upon the identity of the metal bound in the active site: if Ni(II) is bound, the products are off‐pathway, consisting of carbon monoxide 3‐methylthiopropionate and formate. If Fe(II) is bound, the products are formate and 4‐methylthio‐2‐ketobutyrate, the keto‐acid precursor of methionine. It has become clear in recent years that most prokaryotes and eukaryotes have an ARD homolog, and these homologs have been implicated in regulatory and/or signaling functions beyond their role in the methionine salvage pathway. This chapter is a review of structural, mechanistic, and biological aspects of ARD, and highlights the proposed role of Ni in the observed enzymatic activity.