The design of new generation bioprocessing plants is increasingly depe
ndent on the design of process-compatible microorganisms. The latter,
whether through genetic or physiological manipulations, can be greatly
assisted by metabolic engineering. An emerging powerful tool in metab
olic engineering research is computer-assisted cell design using mathe
matical programming. In this work, the problem of optimizing cellular
metabolic networks has been formulated as a Mixed Integer Nonlinear Pr
ogramming (MINLP) model. The model can assist genetic engineers to ide
ntify which cellular enzymes should be modified, and the new levels of
activity required to produce an optimal network, Results are presente
d from the tricarboxylic acid cycle in Dictyostelium discoideum. (C) 1
998 John Wiley & Sons, Inc.