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. 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.
Rodríguez-Prados
Juan-Carlos
JC
Department of Biochemistry and Molecular Biology, University of Barcelona, Spain.
de Atauri
Pedro
P
Maury
Jérôme
J
Ortega
Fernando
F
Portais
Jean-Charles
JC
Chassagnole
Christophe
C
Acerenza
Luis
L
Lindley
Nic D
ND
Cascante
Marta
M
D019295:Computational Biology; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics; D017353:Gene Deletion; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008954:Models, Biological; D015202:Protein Engineering; D011770:Pyruvate Kinase / Q000235:genetics; D049490:Systems Biology; D013912:Threonine / Q000096:biosynthesis*
D029968:Escherichia coli Proteins; D013912:Threonine; D011770:Pyruvate Kinase