SBIR Phase II: Ultra Rapid Genome Engineering in Industrial Yeast Strains

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is the ability to rapidly engineer yeast for production of fuels, chemicals, enzymes, and other valuable molecules. Yeast offers high value production capabilities; however, engineering new strains is very complex and expensive - costing approximately $75-100 million, and requiring 7-10 years for development with current engineering methods. This project will develop a genome engineering technology for yeast that can substantially reduce the cost and time for developing new strains for industrial biotechnology applications. This technology will increase the ability of companies to use yeast to efficiently produce high-quality products from renewable feedstocks, and help grow the overall industrial biotechnology market. This SBIR Phase II project proposes to develop the ability to perform rapid whole-genome engineering in industrial yeast strains. Current technologies to engineer cells for specific functions (e.g., chemical or fuel production) are inefficient, expensive and extremely time consuming. Multiplex Automated Genome Engineering (MAGE) is a disruptive technology that provides a powerful platform to engineer microorganisms at tremendously reduced cost. Until recently, MAGE was limited to a laboratory strain of E. coli, possessing key genetic features that enable MAGE. Recent advances have allowed us to port MAGE to yeast, and the goal of this project is to increase efficiency of the system and endow existing industrial yeasts with the capacity to undergo MAGE. The goal is to improve MAGE efficiency in yeast by developing a high-throughput system to rapidly create and quantify strain variants for their capacity to undergo the MAGE process itself. This project will establish a system to identify and optimize the requisite genetic features for MAGE in yeast, in order to rapidly engineer industrial yeast strains for specific function.