Figure 1.

Schematic illustration of the FVSEOF method with GR constraints. Functionally grouped reactions were considered based on genomic context and flux-converging pattern analyses obtained from the STRING database. FVSEOF was then performed under GR constraints to identify gene amplification candidates for the production of a target chemical. The candidates were evaluated based on the model predictions and additional criteria of the flux bias ( V_avg) and the slope of the flux changes (q_slope). Each rectangle containing a C_xJ_y index and a line with different colors defines the reaction groups that are likely on or off simultaneously, as determined by genomic context and flux-converging pattern analyses. The C_xJ_y index for each reaction is determined by flux-converging pattern analysis. C_x and J_y denote the total number of carbon atoms in metabolites that participate in each reaction and the type of fluxes through the flux-converging metabolites from a carbon source, respectively. The red metabolites indicate flux-converging metabolites. The flux-converging metabolites indicate metabolites at which two pathways split by another metabolite recombine. For example, glyceraldehyde-3-phosphate converges the fluxes split by the fructose-bisphosphate aldolase from the fructose-6-phosphate. The flux-converging metabolites categorize J_y into four types, indicated as J_A, J_B, J_C, and J_D. Each subscript of J_y denotes the number of flux-converging metabolites that are passed zero, one, two, or three times, respectively, for a given flux from a carbon source. The subscript E is specially denoted to indicate the fluxes derived from pyruvate. The values of C_xJ_y for each reaction were assigned based on possible flux routes reaching from glucose, and are partitioned by a slash.