Patent ID: 8594945

Claim:
A method for improving an organism producing a useful substance, the method comprising the steps of: (a) selecting a target organism for producing a target useful substance, and constructing a metabolic network model of the selected target organism; (b) defining a utilization of each of i metabolites in j reactions as a flux sum Φ i = 1 2 ⁢ ∑ j ⁢  S ij ⁢ v j  , wherein Φ i represents the utilization of the i th metabolite, S ij represents the stoichiometric coefficient of the i th metabolite in the j th reaction under the assumption of a quasi-stead state, and v j represents the metabolic flux vector of the j th reaction; (c) selecting a plurality of objective functions, including a function of the formation rate of the useful substance, and additional objective functions other than the formation rate of the useful substance (d) determining a minimum value and a maximum value of the additional objective functions (e) optimizing the objective function of the formation rate of the useful substance within the range between the minimum value and the maximum value of the additional objective functions, (f) determining the flux sum (Φ i ) of each metabolite from the objective functions; (g) clustering and screening a specific metabolite which shows an increase in the flux sum (Φ i ) according to an increase in the formation rate of the target useful substance; (h) selecting genes to be introduced or amplified from a metabolic pathway associated with the specific metabolite screened in the step (g); and (i) constructing a mutant of the target organism by introducing and/or amplifying the genes selected in the step (h) in the target organism.