18-01: Commercialization of a microbial strain for the production of 1,4-butanediol

The biggest challenge to commercialization of industrial bioprocesses for fuels and chemicals is to surpass the ‘promising science’ stage and achieve target metrics of titer, yield, and productivity needed to make the process economically attractive. The literature contains many examples of strains engineered to produce different chemicals of interest; however, few of these ever reach commercialization. Previously at Genomatica, we used a combined computational/experimental approach to engineer E. coli for the production of 1,4-butanediol (BDO) from carbohydrates for the first time (Yim et al., 2011, Nat. Chem. Biol. 7:445-452). BDO is a four-carbon diol currently manufactured exclusively through various petrochemical routes. It 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 benign bioprocesses using renewable feedstocks.

Here we describe how this organism was further engineered for superior performance, scaled to commercial fermentation volumes, and integrated with downstream separations processes to achieve a cost advantaged process relative to petrochemical routes. Systems biology approaches including genome sequencing, transcriptomics, ¹³C-flux analysis, and metabolomics were applied in conjunction with models to characterize the strain and identify targets for further improvement. Synthetic biology, enzyme engineering, high-throughput screening, and fermentation process tuning were used to introduce and optimize these targets. Our presentation will show how this united, multi-disciplinary approach led to significant advances in BDO titer, production rate, and yield that was validated at the commercial scale.