Design of stable metabolic networks

MAGGIO, JIMENA DI; BLANCO, ANÍBAL M.; BANDONI, J. ALBERTO; RICCI, JUAN CARLOS DIAZ; DIAZ, M. SOLEDAD

ENGINEERING IN LIFE SCIENCES

WILEY-V C H VERLAG GMBH

Año: 2017

1618-0240

In this work, we propose eigenvalue optimization combined with Lyapunov theory concepts to ensure stability of the Embden-Meyerhof-Parnas pathway, the pentose-phosphate pathway, the phosphotransferase system and fermentation reactions of Escherichia coli. We address the design of a metabolic network for the maximization of different metabolite production rates. The first case study focuses on serine production, based on a model that consists of eighteen differential equations corresponding to dynamic mass balances for extracellular glucose and intracellular metabolites, and thirty kinetic rate expressions. A second case study addresses the design problem to maximize ethanol production, based on a dynamic model that involves mass balances for twenty-five metabolites and thirty eight kinetic rate equations. The nonlinear optimization problem including stability constraints has been solved with reduced space Successive Quadratic Programming techniques. Numerical results provide useful insights on the stability properties of the studied kinetic models.