S145: The industrialization of synthetic biology for high-throughput strain construction and hypothesis testing

Manipulation of metabolic networks can result in the biosynthesis of numerous novel compounds. While metabolic engineering can offer a sustainable and renewable source of chemicals and fuels, achieving this at an economic, industrial scale is always a challenge. Repeated rounds of strain manipulation spanning multiple years are required before a strain capable of high yields and productivity is found. We would like to present the development of a strain engineering platform that allows high-throughput interrogation of multiple hypotheses in a matter of weeks instead of years. The platform is enabled by a modular molecular biology system which utilizes a series of well-characterized DNA linkers, coupled with computer-aided strain design and robotics to allow error-free manipulation of thousands of DNA parts in a single process. We have been able to successfully deploy automated strain engineering (ASE) towards the construction and assembly of combinatorial DNA libraries, resulting in rapid development of high yielding strains for our candidate fuel and chemical molecules.  We will also present how ASE can be used to rapidly address the complex hypothetical questions often posed by signal pathways and believe that this platform represents a new paradigm for the industrialization of synthetic biology.