In silico strategy to rationally engineer metabolite production: A case study for threonine in Escherichia coli

Genetic engineering of metabolic pathways is a standard strategy to increase the production of metabolites of economic interest. However, such flux increases could very likely lead to undesirable changes in metabolite concentrations, producing deleterious perturbations on other cellular processes. T...

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Published in:Biotechnology and bioengineering 2009-06, Vol.103 (3), p.609-620
Main Authors: Rodríguez-Prados, Juan-Carlos, de Atauri, Pedro, Maury, Jérôme, Ortega, Fernando, Portais, Jean-Charles, Chassagnole, Christophe, Acerenza, Luis, Lindley, Nic D, Cascante, Marta
Format: Article
Language:English
Subjects:
Amino acids
Biological and medical sciences
Biotechnology
Cells
Computational Biology
E coli
Enzymes
Escherichia coli
Escherichia coli - genetics
Escherichia coli - metabolism
Escherichia coli Proteins - genetics
Fundamental and applied biological sciences. Psychology
Gene Deletion
Genetic engineering
metabolic control analysis
metabolic engineering
Metabolic Networks and Pathways - genetics
Metabolism
Metabolites
Models, Biological
Protein Engineering
Pyruvate Kinase - genetics
Sensitivity analysis
Systems Biology
Threonine - biosynthesis
threonine synthesis
universal method
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Summary:Genetic engineering of metabolic pathways is a standard strategy to increase the production of metabolites of economic interest. However, such flux increases could very likely lead to undesirable changes in metabolite concentrations, producing deleterious perturbations on other cellular processes. These negative effects could be avoided by implementing a balanced increase of enzyme concentrations according to the Universal Method [Kacser and Acerenza (1993) Eur J Biochem 216:361-367]. Exact application of the method usually requires modification of many reactions, which is difficult to achieve in practice. Here, improvement of threonine production via pyruvate kinase deletion in Escherichia coli is used as a case study to demonstrate a partial application of the Universal Method, which includes performing sensitivity analysis. Our analysis predicts that manipulating a few reactions is sufficient to obtain an important increase in threonine production without major perturbations of metabolite concentrations. Biotechnol. Bioeng. 2009;103: 609-620.
ISSN:0006-3592
1097-0290
DOI:10.1002/bit.22271