INVESTIGADORES
BANDONI Jose Alberto
congresos y reuniones científicas
Título:
Design of stable large-scale metabolic networks for amino acid production in Escherichia coli
Autor/es:
J. DI MAGGIO; A. BLANCO; A. BANDONI; J.C. DIAZ-RICCI; S. DIAZ
Lugar:
Dalian
Reunión:
Congreso; SCPPE 2013, The 3rd International Conference on Sustainable Chemical Product and Process Engineering; 2013
Institución organizadora:
Dalina Univ. of Technology
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. REFERENCES 1.        Di Maggio, J., Blanco, A.M., Bandoni, J.A., Díaz, M.S. (2009). Design of Stable Large-Scale Metabolic Network. Computer Aided Chemical Engineering (ISSN 1570-7946), 27, 1755-1760. 2.        Matallana, L., Blanco., A. & Bandoni, J. (2008). Eigenvalue optimization techniques for nonlinear dynamic analysis and design. En Ferruh Erdogdu, Optimization in Food Engineering. Ed.; Taylor and Francis Group. 3.        Schmid, J., Mauch, K., Reuss, M., Gilles, E., Kremling, A. (2004). Metabolic design based on a coupled gene expression-metabolic network model of tryptophan production in Escherichia coli. Metabolic Engineering, 6, 364-377. 4.        Waechter, A. & Biegler, L. (2006). On the implementation of an interior point filter line search algorithm for large-scale nonlinear programming. Mathematical Programming, 106, 1, 25-57.