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The advent of genome-scale models of metabolism has laid the foundation for the development of computational procedures for suggesting genetic manipulations that lead to overproduction. In this work, the computational OptKnock framework is introduced for suggesting gene deletion strategies leading to the overproduction of chemicals or biochemicals in E.(More)
We introduce a computational framework termed OptReg that determines the optimal reaction activations/inhibitions and eliminations for targeted biochemical production. A reaction is deemed up- or downregulated if it is constrained to assume flux values significantly above or below its steady-state before the genetic manipulations. The developed framework is(More)
BACKGROUND Geobacter metallireducens was the first organism that can be grown in pure culture to completely oxidize organic compounds with Fe(III) oxide serving as electron acceptor. Geobacter species, including G. sulfurreducens and G. metallireducens, are used for bioremediation and electricity generation from waste organic matter and renewable biomass.(More)
Genomatica has established an integrated computational/experimental metabolic engineering platform to design, create, and optimize novel high performance organisms and bioprocesses. Here we present our platform and its use to develop E. coli strains for production of the industrial chemical 1,4-butanediol (BDO) from sugars. A series of examples are given to(More)
A hybrid optimization framework is introduced to identify enzyme sets and levels to meet overproduction requirements using kinetic models of metabolism. A simulated annealing algorithm is employed to navigate through the discrete space of enzyme sets while a sequential quadratic programming method is utilized to identify optimal enzyme levels. The framework(More)
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