A computational procedure for optimal engineering interventions using kinetic models of metabolism

Francisco G. Vital-Lopez, Antonios Armaou, Evgeni V. Nikolaev, Costas D. Maranas

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The identification of optimal intervention strategies is a key step in designing microbial strains with enhanced capabilities. In this paper, we propose a general computational procedure to determine which genes/enzymes should be eliminated, repressed or overexpressed to maximize the flux through a product of interest for general kinetic models. The procedure relies on the generalized linearization of a kinetic description of the investigated metabolic system and the iterative application of mixed-integer linear programming (MILP) optimization to hierarchically identify all engineering interventions allowing for reaction eliminations and/or enzyme level modulations. The effect of the magnitude of the allowed changes in concentrations and enzyme levels is investigated, and a variant of the method to explore high-fold changes in enzyme levels is also analyzed. The proposed framework is demonstrated using a kinetic model modeling part of the central carbon metabolism of E. coli for serine overproduction. The proposed computational procedure is a general approach that can be applied to any metabolic system for which a kinetic description is provided.

Original languageEnglish (US)
Pages (from-to)1507-1517
Number of pages11
JournalBiotechnology progress
Volume22
Issue number6
DOIs
StatePublished - Nov 1 2006

All Science Journal Classification (ASJC) codes

  • Biotechnology

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