Tuesday, July 28, 2009 - 8:00 AM
S52
The design, engineering, and evolution of microbial catalysts for bio-manufacturing of 1,4-butanediol
Stephen Van Dien, Genomatica, Inc., 10520 Wateridge Circle, San Diego, CA 92121
Genomatica has established a revolutionary suite of computational and experimental technologies to design, create, and optimize novel bioprocesses. This Integrated Metabolic Engineering Platform enables Genomatica to generate proprietary microorganisms with superior performance characteristics, in less time and at a lower cost than current approaches. Here we present the use of our platform to develop E. coli strains for producing the industrial chemical 1,4-butanediol (BDO) from glucose and sucrose. BDO is the key intermediate in a $4.0B family of solvents and polymer precursors that includes gamma-butyrolactone, tetrahydrofuran, pyrrolidone, and N-methylpyrrolidone. Therefore, this product represents an opportunity to replace traditional petrochemical processes with benign bioprocesses using renewable feedstocks.
This presentation will cover the application of Genomatica’s technology platform to design and engineer a microorganism capable of producing this chemical from carbohydrate for the first time. The Biopathway Predictor algorithm was employed to elucidate all possible routes to BDO from central metabolites, and the most favorable pathway chosen. We then used the OptKnock methodology to engineer host metabolism, identifying and implementing gene deletions that couple product formation to growth. Evolutionary engineering is a complementary approach using controlled selection pressure to optimize strain fitness and growth following genetic manipulations. Throughout the host and pathway construction process, metabolic models facilitated data analysis to evaluate performance and find targets for further rounds of strain engineering. Our results clearly demonstrate commercialization potential of this breakthrough biochemical process, and more generally that our novel approach is expediting the metabolic engineering of superior industrial organisms for low-cost chemical production.
This presentation will cover the application of Genomatica’s technology platform to design and engineer a microorganism capable of producing this chemical from carbohydrate for the first time. The Biopathway Predictor algorithm was employed to elucidate all possible routes to BDO from central metabolites, and the most favorable pathway chosen. We then used the OptKnock methodology to engineer host metabolism, identifying and implementing gene deletions that couple product formation to growth. Evolutionary engineering is a complementary approach using controlled selection pressure to optimize strain fitness and growth following genetic manipulations. Throughout the host and pathway construction process, metabolic models facilitated data analysis to evaluate performance and find targets for further rounds of strain engineering. Our results clearly demonstrate commercialization potential of this breakthrough biochemical process, and more generally that our novel approach is expediting the metabolic engineering of superior industrial organisms for low-cost chemical production.
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See more of The Annual Meeting and Exhibition 2009 (July 26 - 30, 2009)
See more of Invited Oral Papers
See more of The Annual Meeting and Exhibition 2009 (July 26 - 30, 2009)