S152: Sustainable Production of Industrial Chemicals Using Microbial Biocatalysts: E. coli and 1,4-Butanediol

Microbial fermentation has proven to be an essential method for producing pharmaceuticals as well as chemicals. Escherichia coli was chosen because of we could quickly engineer the strain, scale fermentation, and have the ability to use various feedstocks. Using its computational/experimental metabolic and genetic engineering platform, Genomatica has designed, developed and optimized E. coli strains for the production of the chemical 1,4-butanediol (BDO) from sugars. BDO is part of a large volume family of solvents and polymer intermediates with an overall market opportunity exceeding $4.0B. Therefore, this product represents an opportunity to make a significant impact on the replacement of traditional petrochemical processes with bioprocesses using renewable feedstocks.

We will describe the application of Genomatica’s technology platform to design and construct a high-performing microorganism capable of producing BDO from carbohydrates. We used our computational tools to elucidate the most favorable pathway to produce this non-natural product, and to engineer the host strain to direct cellular carbon and energy resources into this pathway. Additionally, our modeling platform facilitates the analysis of fermentation data to evaluate performance. Moreover, we use a variety of systems biology approaches including whole genome sequencing, microarrays, ¹³C-flux analysis, proteomics, and metabolomics to implement strain and pathway modifications as well as process improvement. The presentation will show significant progress was made in BDO titer, production rate, and yield through model-guided strain and process improvement, ultimately resulting in an economically attractive process that was validated at the commercial plant scale.