Unusual mechanism of aziridine biosynthesis catalysed by the αKG-dependent non-heme enzyme TqaL

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