SBIR Phase I: Computational Enzyme Design for the Production of Butadiene

This Small Business Innovation Research Phase I project proposes engineering novel biocatalysts for the production of butadiene. High value, renewable chemicals have the potential to become economic drivers for integrated biorefineries. Currently, effectively exploiting biomass is limited by the low specificity of chemical processes and the low catalytic diversity of naturally occurring dehydratases. We will apply a unique and groundbreaking enzyme design technology harnessing computational power to rapidly screen and design novel dehydratases not existing in nature. An ideal dehydratase active site targeting the substrate will be generated and grafted into a large library of proteins. The library will be computationally optimized for high substrate affinity and specificity, with top enzyme models selected for experimental characterization and assayed for catalytic activity. The anticipated result of this SBIR Phase 1 research project is a novel enzyme that converts 2,3-butandiol into butadiene in the test tube. Ultimately, this project will lead to a fermentation process to convert cellulosic sugars directly into butadiene, a higher value, renewable chemical. The broader impact/commercial potential of this project will enable integrated biorefineries to more effectively use biomass, diversify revenue streams and potentially reduce hazardous waste. Our proposed approach, which uses the only proven technology for the design of novel catalytic machineries, will lead to new dehydratases for the production of commercially high value renewable chemicals. Directed evolution, the current state of the art, cannot address the enormous combinatorial complexity inherent in generating novel enzymes. Butadiene is an existing building block used in a wide variety of applications, resulting in a multibillion-dollar market ($5.56M in 2008). Bio-butadiene can be used directly as a renewable drop-in chemical in these existing applications and, therefore, offers an attractive and immediate opportunity to help built a stable and profitable biorefinery industry. Furthermore, the knowledge gained in this project will be leveraged to generate a panel of dehydratase enzymes for the production of other renewable chemicals, thereby opening up the opportunity to access new markets and develop new and innovative products. This technology will help address many of the pressing needs of the biorefinery industry: Develop new biofuels,increase profitability, and accelerate growth through efficient and effective conversion of biomass.