INVESTIGADORES
DIAZ Maria Soledad
congresos y reuniones científicas
Título:
Design of stable large-scale metabolic networks for amino acid production in Escherichia coli
Autor/es:
JIMENA DI MAGGIO; ANIBAL BLANCO; J. ALBERTO BANDONI; JUAN C. DIAZ RICCI; MARIA SOLEDAD DIAZ
Lugar:
Dalian
Reunión:
Congreso; 3rd International Conference on Sustainable Chemical Product and Process Engineering; 2013
Institución organizadora:
Dalian Univ. of Tech., China; Wayne State Univ., USA
Resumen:
The biosynthesis of amino acids mediated by microorganisms has
become an attractive biotechnological process. The advances in
recombinant DNA techniques allow improving product quality and
quantity, through the introduction of a metabolic pathway or the
modification of existing ones, making the process more
competitive from an industrial point of view (Schmid et al., 2004).
Because of the complexity of the cellular metabolism, kinetic
mathematical models that describe the metabolism and its
regulation are of great importance to evaluate the effects of
genetic manipulations or to predict which modifications on
metabolism are required to achieve a given objective, for example
the production of a certain metabolite, by formulating a design
problem. Due to the nonlinear kinetics of the biochemical
reactions and their coupling through common metabolites, biological systems may undergo drastic
changes in their behavior when a variation of the enzyme levels occurs. If no stability constraints are
included in the formulation, the optimal operating point might result unstable, making the network
vulnerable to external disturbances.
In this work, we formulate a design problem for the maximization of tryptophan production based on a
metabolic network model that describes the Embden-Meyerhof-Parnas pathway, the pentose-phosphate
pathway, phosphotranferase system and production of serine and tryptophan of Escherichia coli K-12
W3110 (Schmid et al., 2004; Di Maggio, et al., 2009). We propose an eigenvalue optimization approach
(Matallana et al. 2008) to ensure steady state stability of the optimal flux distribution. The nonlinear
optimization problem, corresponding to steady state equations and additional stability constraints, has
been solved with a reduced space Successive Quadratic Programming techniques within program IPOPT (Waechter & Biegler, 2006). Numerical results provide useful insights on the stability properties of the kinetic model describing the metabolism of E. coli.