Computational Methods for Modification of Metabolic Networks.

In metabolic engineering, modification of metabolic networks is an important biotechnology and a challenging computational task. In the metabolic network modification, we should modify metabolic networks by newly adding enzymes or/and knocking-out genes to maximize the biomass production with minimum side-effect. In this mini-review, we briefly review constraint-based formalizations for Minimum Reaction Cut (MRC) problem where the minimum set of reactions is deleted so that the target compound becomes non-producible from the view point of the flux balance analysis (FBA), elementary mode (EM), and Boolean models. Minimum Reaction Insertion (MRI) problem where the minimum set of reactions is added so that the target compound newly becomes producible is also explained with a similar formalization approach. The relation between the accuracy of the models and the risk of overfitting is also discussed.