Mononuclear nonheme iron enzymes (MNHEs) catalyze a range of very diverse reactions in O(2) metabolism, but they share a common principle active-site organization. To investigate a putative catalytic promiscuity of these enzymatic metal centers, we studied the reactivity of the 3-His ligated metal center of diketone cleaving enzyme (Dke1) toward non-native substrates, with a focus on alternative O(2) dependent reactions. From a screening approach, which aims at eliminating steric factors by including minimal substrate-substructures, three alternative, 'non-β-dicarbonyl-cleavage' reactions are identified, among them an unprecedented oxygenation of maltol. Maltol cleavage is characterized by steady state and fast kinetic measurements and shows an O(2) concentration dependent rate determining step k(cat)/K(M)(O(2)) of 0.3mM(-1)s(-1) and a strict coupling of O(2) reduction and substrate oxidation. Furthermore, the catalytic potential of the 3-His metal center for O(2) dependent catechol ring-cleavage and phenylpyruvate oxidation (PP) is demonstrated.