Abstract 2193 A Rieske Catalytic Journey

Rieske oxygenases are characterized by the presence of two metallocenters, a [2Fe-2S] cluster and a mononuclear iron site. This set of metallocenters, in coordination with molecular oxygen, create a high valent Fe-based oxidant that can be used to facilitate monooxygenation, dioxygenation, and other types of chemical reactions. Remarkably, despite this extensive catalytic repertoire, Rieske oxygenases demonstrate exquisite control in differentiating between these reaction types to ensure that only the intended transformation is catalyzed. This precision is demonstrated in a number of biosynthetic pathways that produce medically and industrially relevant natural products, as well as in pathways that degrade xenobiotic compounds. However, the molecular details that enable these enzymes to catalyze site-specific reactions with diverse outcomes remain largely enigmatic. Therefore, in this presentation, I will highlight our progress toward identifying the structural trends that Rieske oxygenases employ to dictate selective reaction outcomes. The work in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R35 GM138271 (J.B.-R.).