Invited Talk 21st International Conference on Biological Inorganic Chemistry 2025

Discovery and study of non-heme Fe radical halogenases (122803)

Michelle Chang 1
  1. Princeton University, Princeton, NJ, United States

Living systems have evolved the capacity to carry out many chemical transformations of interest to synthetic chemistry if they could be redesigned for targeted purposes.Our lab has focused on the study of Fe(II)/alpha-ketoglutarate-dependent radical halogenases for their ability to carry out C-H activation followed by functionalization with native (X = Cl) and non-native (X = Br, N3, etc) anions. Exploration of enzymes from the BesD amino acid halogenase family has allowed us to identify members with differing reaction pathway selectivities (hydroxylation vs halogenation), substrate selectivity, and regioselectivity, enabling mechanistic studies to study reaction partitioning between hydroxylation and halogenation as well as substrate selectivity and regioselectivity. These studies enable the engineering of enzymes and pathways to make various halogenated products such as heterocycles, diamines, α-ketoacids, and peptides as well as non-canonical amino acids.