DAD: A Novel Reaction or an Old Dog with New Tricks

Carbon-carbon bond cleavage remains a frequently difficult synthetic task, yet nature is built upon the making and breaking of carbon-carbon bonds through enzyme-catalyzed reactions. One example, 2,4’-dihydroxyacetophenone dioxygenase (DAD), catalyzes the oxidative cleavage of the α-hydroxyketone side-chain of 2,4’-dihydroxyacetophenone (DHAP). While this enzyme has only been cursorily investigated, the DAD reaction bears notable similarity to the cleavage performed by the better understood, acireductone dioxygenase (ARD’). Results of steady-state kinetic experiments and metal-replacement studies of DAD, along with structural and sequence comparisons, will be used to present a case that the DAD and ARD’ reactions are only superficially similar.