A pressing challenge facing society is the development of sustainable energy sources. In this context, hydrogen has emerged as a possible clean alternative to carbon-based fuels, if scalable and environmentally friendly methods for its production and utilization can be developed. A potentially cost-effective and environmentally sound route to hydrogen can gleaned from nature: A family of specialized enzymes called hydrogenases catalyzes proton reduction as well as hydrogen oxidation in mild conditions, using base metals such as iron at the active site. The most efficient ones for hydrogen production, the [FeFe] hydrogenases, incorporate a small diiron organometallic complex and force it into a thermodynamically unstable, but catalytically active conformation, through crucial protein contacts. Understanding how the protein environment accomplishes this feat could have transformative effects on the design of artificial redox enzymes. Bioinspired organometallic complexes have clarified many mechanistic aspects of proton reduction, but have not reached the efficiency of the natural enzyme due to limitations on the incorporation of second-sphere and long-range interactions. Here, we propose a hybrid system by which the chemistry of simple, relatively inefficient organometallic centers can be enriched through second-sphere and long-range interactions provided by a protein scaffold. Our unique strategy is built around the use of unnatural amino acids with dithiol side chains within a protein core that can coordinate and stabilize diiron sites of bioinspired organometallic catalysts. Using this strategy we have demonstrated nascent hydrogen production activity by small peptide-based model systems in water at near-neutral pH. We will now (1) expand our synthetic methodologies to prepare a family of artificial amino acids, (2) develop prototype de novo designed artificial hydrogenases, (3) use computational protein design concomitantly with (4) directed evolution methods to optimize second coordination sphere and long range interactions. The Intellectual Merit of the project is that it harnesses the rich diversity of function of organometallic complexes, augmenting it with state of the art evolutionary and computational methods to optimize second coordination sphere and long-range interactions. Our approach provides a means to test natural hydrogenase mechanisms while generating blueprints to develop novel ones. The development of evolvable protein-based hybrid catalysts capable of producing fuel in a sustainable manner directly addresses an urgent global need. Beyond hydrogen production, this project will establish a procedure to develop hybrid catalysts that will be widely applicable to a variety of chemical reactions, including those not occurring in nature, with the potential to impact the production of high-value chemicals. The Broader Impacts of this proposal are twofold. First, the project relies on a highly interdisciplinary approach, which offers students at the graduate and undergraduate level a rich training in modern bioinorganic chemistry. Second, as an active participant in the IGERT training grant (SUN- Solar Utilization Network), the PI has partnered with the Arizona Science Outreach Foundation, a student-led organization that conducts science workshops in schools throughout the Phoenix area. The PI will continue to coordinate a group of IGERT student to prepare and carry out teaching modules designed to adhere to the Arizona 6th grade science standards and to introduce concepts related to sustainable energy in the classrooms.
|Effective start/end date||9/1/15 → 8/31/19|
- National Science Foundation (NSF): $473,529.00
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