Overview of Amino Acid Modifications by Iron- and ?-Ketoglutarate- Dependent Enzymes

Modified amino acids are important building blocks in both natural biomolecules and synthetic small-molecule drugs. Here, we review the roles of iron-and alpha-ketoglutarate-dependent dioxygenases in the oxidative modification of amino acids, focusing on C-H hydroxylation and halogenation. Recent engineering approaches to alter substrate specificity, improve catalytic efficiency, and install non-native activities are also discussed, along with several applications in complex molecule synthesis. We conclude with a brief discussion on recent discoveries of unique oxidative cyclization activities on amino acids by several family members and contemporary challenges in expanding both the biocatalytic utility and the reaction scope of the enzyme family.