Unusual Mechanism of Aziridine Biosynthesis Catalysed by an αKGdependent Non-heme Enzyme TqaL

Aziridines are present in many synthetic pharmaceuticals. The synthesis of aziridine ring remains challenging due to its highly strained three-membered ring structure. Recently, a non-heme αKG-dependent enzyme TqaL have been demonstrated to catalyze the synthesis of aziridines from L-Val. However, the detailed reaction mechanism of the enzyme remains elusive. Here, we report, the mechanism of oxidative cyclisation for aziridine synthesis catalyzed by TqaL. Following the hydrogen atom abstraction step, the reaction proceeds via a unique concerted process with single electron transfer from the isopropyl radical to the Fe(III)-OH motif, which is coupled with the electrophilic attack of the primary amine substrate to the tertiary isopropyl radical and simultaneous proton transfer from the substrate amine to the hydroxyl group of the Fe(III)-OH to give aziridine. This research would provide valuable structural basis for tailoring the non-heme αKG-dependent enzyme for the biosynthesis of highly active aziridinederivatives as pharmaceuticals.