Jennifer Bridwell-Rabb

University of Michigan

March 4, 2020 (Wed.)
11:00 – 11:50 am
C 121

Rieske non-heme iron Oxygenases in Natural Product Biosynthesis 

Abstract:

Rieske oxygenases harness the reactivity of transition metals to perform powerful, efficient, and site-specific transformations of traditionally inert bonds. These enzymes, which couple a [2Fe-2S] cluster with a non-heme iron site, exploit molecular oxygen (O2) as a co-substrate and function as dioxygenases or monooxygenases, and have even been shown to catalyze sequential monooxygenation reactions. As demonstrated in a number of biosynthetic pathways that produce natural products with antibiotic, antifungal, anticancer, or anesthetic activities, as well as in pathways that degrade environmental pollutants, these enzymes demonstrate exquisite control in differentiating between these reaction types to ensure that only the intended transformation is catalyzed. Thus, these enzymes represent a valuable source of enzymatic strategies to industrially produce pharmaceuticals and commodity chemicals, or facilitate bioremediation efforts. However, there is a critical lack of information available about how these enzymes use a common set of metallocenters to catalyze site-specific reactions with diverse outcomes. Therefore, we will uncover the architectural strategies that Nature uses to tune the selectivity and catalytic repertoire of the Rieske oxygenase enzymes. This knowledge will provide predictive power towards repurposing Rieske oxygenases to catalyze custom reactions, and will support efforts to exploit their chemistry for a wide variety of biotechnological endeavors.