Aziridine Formation by a FeII/α‐Ketoglutarate Dependent Oxygenase and 2‐Aminoisobutyrate Biosynthesis in Fungi

Abstract

AbstractAziridine is a characteristically reactive molecule with increased bioactivity due to its strained ring structure. Here, we investigated the biosynthesis of 2‐aminoisobutyric acid (AIB) in Penicillium, and successfully reconstituted the three‐step biosynthesis from L‐Val to AIB in vitro. This previously unknown aziridine formation pathway proceeded with the non‐heme iron and α‐ketoglutarate‐dependent (FeII/αKG) oxygenase TqaL, followed by aziridine ring opening by the haloalkanoic acid dehalogenase (HAD)‐type hydrolase TqaF, and subsequent oxidative decarboxylation by the NovR/CloR‐like non‐heme iron oxygenase TqaM. Furthermore, the X‐ray crystal structure of the C−N bond forming FeII/αKG oxygenase TqaL was solved at 2.0 Å resolution. This work presents the first molecular basis for aziridine biogenesis, thereby expanding the catalytic repertoire of the FeII/αKG oxygenases. We also report the unique aziridine ring opening by a HAD‐type hydrolase and the remarkable oxidative decarboxylation by a non‐heme iron oxygenase to produce AIB.