Follow the spectra: Mapping electronic structure to reactivity in metalloproteins

Metalloenzymes catalyze the challenging chemical reactions that lie at the core of vital life processes, from carbon and nitrogen fixation to photosynthesis and respiration. Native metalloenzymes use only earth-abundant transition metals and operate under mild conditions, accessing reactivity that remains largely out of reach for synthetic systems. Given the importance of these fundamental processes in the context of energy, environment, sustainability, and human health, gaining molecular-level understanding into how metalloenzymes work is of the utmost importance. To this end, we are developing protein-based models as structural, functional, and mechanistic mimics of naturally occurring metalloenzymes. Nickel-containing, multimetallic enzymes such as hydrogenase, carbon monoxide dehydrogenase (CODH), and acetyl coenzyme A synthase (ACS) are implicated in chemoautotrophic origins of life and play key roles in the metabolisms of ancient bacteria and archaea. However, the molecular mechanisms of catalysis remain relatively poorly understood, thwarting efforts to build biomimetic synthetic systems that act with the efficacy of native enzymes. We are also interested in understanding how Nature can harness the potent but green oxidant, O2, for selective C-H bond activation. Towards this end, we are exploring novel functionality within a heterobimetallic manganese-iron protein, expanding the capacity of this unique cofactor. In this presentation, our recent efforts to install and characterize novel reactivity in model protein scaffolds will be discussed. By combining functional studies of our model proteins with diverse spectroscopic techniques and computational investigations, we can obtain a comprehensive understanding of how the electronic and geometric structures dictate reactivity in each system. Looking forward, we hope to apply these principles towards engineering effective systems for selective energy conversion reactions while learning about fundamental chemical transformations.

Speaker: Hannah Shafat, UC Los Angeles