Predicting synthetic rescues in metabolic networks - PubMed (original) (raw)

Figure 4

The impact of rescue deletions for E. coli (A, B) and S. cerevisiae (C, D) gene-deficient mutants. (A, C) Predicted biomass production before (○) and after (•) rescue deletions in glucose minimal media. The mutants are generated through the deletion of the genes shown at the _x_-axis. We show the results for all mutants with _G_1MOMA<_G_1FBA such that _G_1MOMA≤0.8 _G_wtFBA and _G_1FBA≥0.2 _G_wtFBA. If the rescue deletion changes the growth rate from zero to some positive value, we observe the Lazarus effect, applying to suboptimally essential genes (left). If the rescue deletion only enhances the growth rate, we observe a suboptimal recovery (right). The experimental information on the lethality of the original E. coli (Edwards and Palsson, 2000; Gerdes et al, 2003; Baba et al, 2006; PEC, 2007) and S. cerevisiae (Giaever et al, 2002; Steinmetz et al, 2002; SDG, 2007) gene-deficient mutants is indicated with (+) for viable mutants, (−) for non-viable mutants, and (a) for a gene absent in the databases. (B, D) Same as in (A, C) for single-gene rescue deletions in various media. We show selected mutants with significant biomass improvements after the rescue deletion of a single gene. The rescue deletion is indicated at the top, and the tested media are indicated at the bottom. The abbreviations stand for acetate (Ac), α-ketoglutarate (Akg), arabinose (Ara), ethanol (Eth), galactose (Gal), glucose (Glc), glucose anaerobic (Glca), glycerol (Gly), lactate (Lac), malate (Mal), mannose (Man), pyruvate (Pyr), rich medium (Rich) (see Supplementary Information), sorbitol (Sor), succinate (Succ), sucrose (Suc), and xylose (Xyl). The biomass fluxes are normalized by the wild-type flux _G_wtFBA in all panels. In units of mmol/g DW-h, the wild-type fluxes for E. coli are 0.187 (Ac), 0.535 (Akg), 0.745 (Ara), 0.908 (Glc), 0.367 (Lac), 0.388 (Mal), 0.908 (Man), 0.303 (Pyr), 2.87 (Rich), 0.418 (Succ), and 1.37 (Suc), while for S. cerevisiae they are 0.189 (Ac), 0.311 (Eth), 0.703 (Gal), 0.819 (Glc), 0.180 (Glca), 0.532 (Gly), 1.34 (Rich), 0.798 (Sor), and 0.742 (Xyl). All the genes involved in the rescues of (A, C) are listed in Supplementary Information, while the minimum rescue sets are listed in Supplementary Tables SII and SIII, respectively. The alternative rescue genes for each media in (B, D) are listed along with the corresponding recoveries in Supplementary Information.