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

Juan-Carlos Rodríguez-Prados, Pedro de Atauri, Jerome Maury, Fernando Ortega, Jean-Charles Portais, Christophe Chassagnole, Luis Acerenza, Nic D. Lindley, Marta Cascante

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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. © 2009 Wiley Periodicals, Inc.
Original languageEnglish
JournalBiotechnology and Bioengineering
Volume103
Issue number3
Pages (from-to)609-620
ISSN0006-3592
DOIs
Publication statusPublished - 2009
Externally publishedYes

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