BTG13-related metalloenzymes: Atypical non-heme iron-dependent dioxygenases with unusual coordination patterns and catalytic mechanisms

Owing to their diverse coordination patterns and catalytic mechanisms, non-heme iron-dependent dioxygenases catalyze a variety of biochemical reactions involved in the synthesis of numerous natural products and valuable compounds. Recently, we discovered a novel and atypical non-heme iron-dependent dioxygenase, BTG13, that features a unique coordination center consisting of four histidines and a carboxylated lysine (Kcx). This enzyme catalyzes the C–C bond cleavage of anthraquinone through two unconventional steps, with modified Kcx playing a key role in facilitating these processes, as revealed by molecular dynamics simulations and quantum chemical calculations. Phylogenetic analyses and other studies suggest that BTG13-related metalloenzymes are widespread in various organisms. Here, we highlight the significance of this new class of non-heme iron-dependent oxygenases and their potential as novel tools for practical applications in synthetic biology.