(481b) Sustainable Production of Industrial Chemicals Using Microbial Biocatalysts: 1,4-Butanediol

Oil and natural gas are used as the primary raw materials for manufacturing an astonishing array of large volume chemicals, polymers, and other products that improve our overall standard of living.  Growing concerns over the environment and volatile fossil energy costs have inspired a quest to develop more sustainable processes that afford these same products from renewable feedstocks with lower cost, energy consumption, and greenhouse gas emissions.  Metabolic engineering of microorganisms is a powerful approach to address this need. Chemical Engineers are at the forefront of this emerging industry, contributing expertise in areas such as computational biology, fermentation process development, and commercial plant design.

A recent success story in sustainable chemical process development is Genomatica’s production of the industrial chemical 1,4-butanediol (BDO) using engineered strains of Escherichia coli. BDO is a chemical intermediate that goes into a range of products including automotive, electronics and apparels (such as spandex), and is currently only commercially made through energy intensive petrochemical processes from hydrocarbon feedstocks.  Nearly three billion pounds of this chemical are produced every year throughout the world, creating a market that is on the order of approximately $4B. It is also converted into derivative solvents and polymer intermediates such as gamma-butyrolactone (GBL) and tetrahydrofuran (THF).Therefore, this product represents an opportunity to make a significant impact on the replacement of traditional petrochemical processes with bioprocesses using renewable feedstocks.

Genomatica has established an integrated suite of computational and laboratory technologies to design, create, and optimize novel organisms and bioprocesses. This presentation will cover the application of this integrated technology platform to design, construct, and optimize a high-performing microorganism capable of producing BDO from carbohydrate feedstocks. The major considerations in engineering strains for chemical production are the biochemical pathway that produces the compound of interest from native metabolites, and the host central metabolism, which must direct cellular resources to this pathway. The Biopathway Predictor algorithm was designed to elucidate virtually all possible routes to BDO from central metabolites, and the most favorable pathway chosen by various criteria. To engineer host strain metabolism, we utilized a genome-scale model of metabolism to identify a set of gene deletions designed to couple product formation to growth. After constructing the host and pathway based on the design, our models facilitated the analysis of fermentation and ‘omics’ data to evaluate performance, thus finding targets for further rounds of strain engineering. The presentation will show how significant progress was made in BDO titer, production rate, and yield through model-guided strain improvement, ultimately resulting in an economically attractive process that was validated at the pilot and demonstration scale.