As an important isoprenoid, lycopene overproduction is a textbook example in metabolic engineering. In E. coli, overproducing farnesyl pyrophosphate (FPP) is critical for increasing the product yield of lycopene because FPP is the native precursor in lycopene biosynthesis (Alper et al., 2005). Herein, we presented the analysis of FPP (frdp[c]) as the Targeted product for overproduction in the UP Finder (Fig. 2). By loading the constraint-based model of E. coli iJO1366 in the Organism item, the output presented key pathway/gene targets for overexpression toward FPP overproduction in E. coli. As shown in Fig. 3, ten metabolic reactions (9 genes involved) were identified as the key pathways for FPP overproduction. The identified reactions were ordered by their associated Ratio values, which can be used as a quantitative evaluation for the overexpression preference. According to this ranked preference for gene overexpression, it was observed that the higher preferred gene targets showed the closer metabolic distance to the targeted product (FPP), which represented the higher relevance to the related overproduction. Compared with the reported key genes for FPP/lycopene overproduction in the literatures (Wang et al., 2009), results from the UP Finder identified all 9 key genes in isoprenoid biosynthesis that directly related to FPP overproduction, showing 100% identity. Also, comparing to the key genes identified by FSEOF (Choi et al., 2010), those gene targets in central carbon metabolic metabolism were not included in the results of UP Finder (Table 1).Fig. 3Analysis results from the UP Finder for farnesyl pyrophosphate (FPP) overproduction in E. coli. Identified gene targets are also shown in the metabolic pathway of FPP biosynthesis presented with gene overexpression preference toward FPP overproduction. GAP, glyceraldehyde-3-phosphate; DXP, 1-deoxy-D-xylulose 5-phosphate; MEP, 2-C-methyl-D-erythritol 4-phosphate; CDP-ME, 4-diphosphocytidyl-2-C-methyl-D-erythritol; CDP-MEP, 4-diphosphocytidyl-2C-methyl-D-erythritol-2-phosphate; MEC, 2C-methyl-D-erythritol-2,4-cyclodiphosphate; HMBPP, (E)−4-hydroxy-3-methylbut-2-enyl-diphosphate; IPP, isopentenyl diphosphate; DMAPP, dimethylallyl diphosphate; GPP, geranyl pyrophosphate; FPP, farnesyl pyrophosphate. dxs, 1-deoxy-D-xylulose-5-phosphate synthase; dxr, 1-deoxy-D-xylulose reductoisomerase; ispD, 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase; ispE, 4-(cytidine 5′-diphospho)−2-C-methyl-D-erythritol kinase; ispF, 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase; ispG, 2C-methyl-D-erythritol 2,4 cyclodiphosphate dehydratase; ispH, 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase; idi, isopentenyl-diphosphate D-isomerase; ispA, geranyltranstransferase (farnesyl diphosphate synthase); crtE, GGPP synthase, crtB, phytoene synthase; crtI, phytoene desaturase. See Supplementary Table S1–S2 for the abbreviations of reaction and metabolite names shown in the UP Finder results.Fig. 3Table 1Comparison of identified gene targets for overproducing lycopene precursor (farnesyl pyrophosphate, FPP) in E. coli.Table 1Reported key genes (Wang et al., 2009)Identified key genes by UP FinderIdentified key genes by FSEOF (Choi et al., 2010)dxsdxsdxsdxrdxrdxrispDispDispDispEispEispEispFispFispFispGispGispGispHispHispHidiidiidiispAispAispApgipfkABfbaAtpiAgltAacnABicdAsucABsucCDsdhABCDfumABmdh