Non-heme Fe enzymes are involved in various natural product biosynthetic pathways. In our study of nucleoside antifungal biosynthesis, we discovered a series of homologous Fe and 2-oxoglutarate (2OG) dependent enzymes that catalyze unusual chemical transformations. For example, PolK and MalI are a dual-function hydroxylase/oxidase, while PolD catalyzes an unusual C-C bond cleavage reaction (see Nat. Chem. Biology. 2021 and ACS Chem. Biol. 2022). The nucleoside pathways also have several functionally uncharacterized putative non-heme Fe enzymes. Thus, we are studying the catalytic functions, mechanisms, and structures of these enzymes with the goal of understanding how these enzymes control the initiation and reactivities of highly oxidative ferryl-oxo and substrate radical species.
Department of Biochemistry, Duke University School of Medicine
