Figure 2

Framework of the FVSEOF with GR constraints for identifying gene amplification targets that enhance the production of a target product. The FVSEOF method scans the changes in the metabolic flux variabilities in response to an enhanced flux toward a target product. The method then selects amplification target reactions, the fluxes of which increase in response to the forced increase in the flux toward the target bioproduct. ( A) During the FVSEOF implementation, three types of intracellular flux profiles are typically identified: increased, decreased, or unchanged, but oscillatory flux profiles can also be found in some cases. ( B) To evaluate the gene amplification candidates, the slope ( q _slope ) was calculated based on a linear regression between the enforced production rate of a target product and the V _avg values of the candidate reactions. The positive correlation in the slope indicates that the corresponding reaction may be a gene amplification candidate. On the basis of the q _slope values, we considered the sensitivities of the identified gene amplification candidates to the enforced production of a target chemical. A large value of q _slope indicates that the corresponding reaction may be more sensitive to the enforced production of a target chemical, than reactions with smaller q _slope values.