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Genome-scale metabolic network models can be reconstructed for well-characterized organisms using genomic annotation and literature information. However, there are many instances in which model predictions of metabolic fluxes are not entirely consistent with experimental data, indicating that the reactions in the model do not match the active reactions in(More)
Genome-scale metabolic models have proven highly valuable in investigating cell physiology. Recent advances include the development of methods to extract context-specific models capable of describing metabolism under more specific scenarios (e.g., cell types). Yet, none of the existing computational approaches allows for a fully automated model extraction(More)
Metabolic engineering modifies cellular function to address various biochemical applications. Underlying metabolic engineering efforts are a host of tools and knowledge that are integrated to enable successful outcomes. Concurrent development of computational and experimental tools has enabled different approaches to metabolic engineering. One approach is(More)
The development and validation of new methods to help direct rational strain design for metabolite overproduction remains an important problem in metabolic engineering. Here we show that computationally predicted E. coli strain designs, calculated from a genome-scale metabolic model, can lead to successful production strains and that adaptive evolution of(More)
BACKGROUND Microorganisms possess diverse metabolic capabilities that can potentially be leveraged for efficient production of biofuels. Clostridium thermocellum (ATCC 27405) is a thermophilic anaerobe that is both cellulolytic and ethanologenic, meaning that it can directly use the plant sugar, cellulose, and biochemically convert it to ethanol. A major(More)
Constraint-based metabolic models are currently the most comprehensive system-wide models of cellular metabolism. Several challenges arise when building an in silico constraint-based model of an organism that need to be addressed before flux balance analysis (FBA) can be applied for simulations. An algorithm called FBA-Gap is presented here that aids the(More)
  • Matthew S. Bienick, Katherine W. Young, Justin R. Klesmith, Emily E. Detwiler, Kyle J. Tomek, Timothy A. Whitehead +1 other
  • 2014
In exponentially growing bacteria, expression of heterologous protein impedes cellular growth rates. Quantitative understanding of the relationship between expression and growth rate will advance our ability to forward engineer bacteria, important for metabolic engineering and synthetic biology applications. Recently, a work described a scaling model based(More)
The generation of well-characterized parts and the formulation of biological design principles in synthetic biology are laying the foundation for more complex and advanced microbial metabolic engineering. Improvements in de novo DNA synthesis and codon-optimization alone are already contributing to the manufacturing of pathway enzymes with improved or novel(More)
Symbiotic interactions between organisms are important for human health and biotechnological applications. Microbial mutualism is a widespread phenomenon and is important in maintaining natural microbial communities. Although cooperative interactions are prevalent in nature, little is known about the processes that allow their initial establishment, govern(More)