Directed Evolution of an Iron(II)‐ and α‐Ketoglutarate‐Dependent Dioxygenase for Site‐Selective Azidation of Unactivated Aliphatic C−H Bonds**

FeII- and α-ketoglutarate-dependent halogenases oxygenases can catalyze site-selective functionalization of C−H bonds via a variety C−X bond forming reactions, but achieving high chemoselectivity for using non-native functional groups remains rare. The current study shows that directed evolution be used to engineer variants the dioxygenase SadX address this challenge. Site-selective azidation succinylated amino acids amine was achieved as result mutations throughout structure. installed azide group reduced primary amine, succinyl required enzymatically cleaved provide corresponding amine. These results promising starting point evolving additional with activity on structurally distinct substrates enabling enzymatic other groups.