The development of platform-based technologies for the optimization of sustainably produced chemicals

Genomatica has established an integrated computational/experimental metabolic engineering platform to design, create, and optimize novel high-producing organisms and bioprocesses. Here we present the use of our platform to develop E. coli strains for the production of the industrial chemical 1,4-butanediol (BDO) from carbohydrate feedstocks. These efforts have culminated in commercial scale production  of over 5M lbs of BDO from dextrose. BDO is a chemical intermediate (>3B lbs/yr) that goes into a variety of products including automotive, electronics and apparel (such as spandex), and is currently produced commercially through energy-intensive petrochemical processes using hydrocarbon feedstocks. Therefore, this product represents an opportunity to make a significant impact on the replacement of traditional petrochemical processes with benign bioprocesses using renewable feedstocks.

We are continuing to enhance our technology platform, enabling faster development of new processes with increased chance of success. Here we describe the application and development of one such new technology, cell-free transcription-translation (TX-TL), towards improving the design-build-test-learn cycle for the construction of a high-performing microorganism capable of producing BDO and other industrial chemicals from carbohydrates. We used systems biology approaches including ¹³C-flux analysis, proteomics, and metabolomics to characterize the production of BDO in TX-TL as compared to traditional fermentation processes. The presentation will highlight the successful integration of the TX-TL technology into our rational and high-throughput strain engineering platform, and will show the potential advantages for using cell-free systems towards the optimization of sustainably produced chemicals.