STTR Phase I: Synthetic Biology 2.0: A platform for the automated design of cell factories incorporating synthetic enzymes

This Small Business Technology Transfer (STTR) Phase I project brings together computational enzyme design with systems biology to create a fully integrated platform for novel pathway designs. The approach chosen will combine specific databases and a novel pathway synthesis tool. This computational tool will use the information present in the databases to automatically discover, or "design", novel pathways for fermenting natural renewable feedstock to virtually any chemical of human interest. In the Phase II Experimental Plan, the goal is to further advance the concept by developing a high-performance pathway prioritization module to estimate each designed pathway yield and impact on organism metabolism, and experimentally test the performance of the system. To our knowledge, the proposed research is the first attempt of combining computational enzyme design with computational pathway prospecting and modeling. The broader impact/commercial potential of this project, if successful, will be to engineer biosystems and cell factories for industrial applications, especially in the field of bio-based chemicals and biofuels. Most successes to date in the field of synthetic biology have involved recombining natural enzyme building blocks into novel pathways. However, recent developments in computational enzyme design make it possible to have designer enzymes to enhance nature's catalytic repertoire. Being able to have an automated, computer-aided design tool that leverages new capabilities to create novel metabolic pathways employing synthetic enzymes will bring us closer to truly synthetic biology.