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 ( Vavg) and the slope of the flux changes (qslope). Each rectangle containing a CxJy 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 CxJy index for each reaction is determined by flux-converging pattern analysis. Cx and Jy 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 Jy into four types, indicated as JA, JB, JC, and JD. Each subscript of Jy 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 CxJy for each reaction were assigned based on possible flux routes reaching from glucose, and are partitioned by a slash.
Park et al. BMC Systems Biology 2012 6:106 doi:10.1186/1752-0509-6-106