Optimization ofbiochemicalsystemsthroughmathematicalprogramming:Methods and applications

In thisworkwepresentageneral(monoandmultiobjective)optimizationframeworkforthetechno- logical improvementofbiochemicalsystems.Thestartingpointofthemethodisamathematicalmodel in ordinarydifferentialequations(ODEs)oftheinvestigatedsystem,basedonqualitativebiological knowledge andquantitativeexperimentaldata.Inthemethodwetakeadvantageofthespecialstructural features ofafamilyofODEscalledpower-lawmodelstoreducethecomputationalcomplexityofthe optimization program.Inthisway,thegeneticmanipulationofabiochemicalsystemtomeetacertain biotechnological goalcanbeexpressedasanoptimizationprogramwithsomedesiredpropertiessuchas linearity orconvexity. The generalmethodofoptimizationispresentedanddiscussedinitslinearandgeometricprogramming versions. Wefurthermoreillustratetheuseofthemethodbyseveralrealcasestudies.Weconcludethat the technologicalimprovementofmicroorganismscanbeaffordedusingthecombinationofmathematical modelling andoptimization.Thesystematicnatureofthisapproachfacilitatestheredesignofbiochemical systems andmakesthisapredictiveexerciseratherthana trial-and-error procedure.