Harnessing Metabolism for Sustainable Production of Chemicals: From Systems Biology to Commercial Scale Manufacturing

Harnessing Metabolism for the Sustainable Production of Chemicals: From

Systems Biology to Commercial Scale Manufacturing

Oil and natural gas are used as the primary raw materials for manufacturing a wide range of large volume chemicals, polymers, and other products. Growing concerns over the environment and volatile fossil energy costs have led to efforts to develop more sustainable processes that can result in these same products made from renewable feedstocks with lower cost, energy consumption, and greenhouse gas emissions. Metabolic engineering of microorganisms is a powerful approach to address this need.
Genomatica has developed a complete bioprocess for the production of 1,4-butanediol (BDO) from carbohydrate feedstocks. 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.
An enabling feature of Genomaticaâ??s process is the microorganism. E. coli has been engineered for high level production of BDO from a range of sugars with high rate and titer and very few by-products. Achieving such high level performance involved detailed engineering of the pathways and the metabolic network in order to entice the organism to channel its precious cellular resources into BDO production. For example, eliminating by-products sounds straightforward (simply delete genes in the by-product pathway), but often perturbs metabolism in unexpected ways. Our systems-based approach to organism engineering provided critical insights about redox and energy metabolism and revealed the path forward to higher level BDO production and a much more robust strain. The importance of taking a step back and performing well-designed diagnostic experiments will be emphasized. These efforts have culminated in commercial scale production of over 5 M lbs of BDO from dextrose.
Conventional sugars such as corn dextrose and sugar cane-derived sucrose are considered staples of the food chain. Accordingly, non-food biomass-derived sugars have emerged as an important feedstock for chemicals and fuels. However, uptake and utilization of biomass sugars such as xylose, arabinose, and prominent hydrolysate polysaccharides requires different metabolic pathways with a unique set of constraints. Again, our systems-based platform proved invaluable in deciphering the metabolic bottlenecks and opening the gates to improved performance.
This presentation will cover the development of a complete bioprocess for commercial scale production of BDO. Systems biology and diagnostic experiments will be emphasized to highlight the importance of rational metabolic engineering approaches for achieving high level strain performance.