Fig. 3
The pathways, genes and reactions modified in this study. A) The mevalonate pathway. The additional copies of native genes (blue shaded) and the heterologous genes (orange shaded) integrated in a previous study to construct the parent strain LRS6 [23] are highlighted. B Fatty acid biosynthesis in mitochondria C Glyoxylate cycle D Connected pathways; branched-chain amino acid biosynthesis (from two pyruvate molecules to L-valine or L-leucine), pantothenate pathway (from 3-methyl-2-oxobutanoate a 5,10-methylenetetrahydrofolate to pantothenate) and the spermidine biosynthesis (from S-adenosyl-L-methionine to spermidine) E de novo purine biosynthesis. The red crosses indicate corresponding gene deletions suggested by the design algorithms; thick arrows highlighted with green colour indicate the corresponding overexpressed genes suggested by the design algorithms. The arrows show the direction of the fluxes. Dashed arrows indicate multiple reactions. A-CoA: acetyl-CoA, AA-CoA: acetoacetyl-CoA, HMG-CoA: hydroxymethylglutaryl-CoA, MEV: mevalonate, MEV-P: R-5 phosphomevalonate, MEV-PP: R-5-diphosphomevalonate, IPP: isopentenyl diphosphate, DMAPP: dimethylallyl diphosphate, GPP: geranyl diphosphate, FPP: farnesyl diphosphate, FOH: farnesol, GGPP: geranylgeranyl diphosphate, TXN: taxadiene, T5α-ol: taxa-4(20),11-dien-5α-ol, T5αAc: taxa-4(20),11-dien-5-α-yl acetate, Mal-CoA: malonyl-CoA, Mal-ACP: malonyl-ACP, 3-KA-ACP: 3-ketoacyl-ACP, 3-hydroxyacyl-ACP, t2-E-ACP: trans-2-enoyl-ACP, OAA: oxaloacetic acid, 2-A-Lac: 2-acetolactate, diOH-M-B: 2,3-dihydroxy-3 methylbutanoate, 3MOB: 3-methyl-2-oxobutanoate, 2-DHP: 2-dehydropantoate, Pnto: R-pantothenate, P-Pan: R- 4’ phosphopantothenate, P-Pan-Cys: R- 4’ phosphopantothenoyl-L-cysteine, Pan-4P: 4’-phosphopantetheine, DP-CoA: 3’-dephospho-CoA, PRPP: 5-Phospho-alpha-D-ribose 1-diphosphate, PRAm: 5-Phospho-beta-D-ribosylamine, GAR: N1-(5-Phospho-D-ribosyl) glycinamide, FGAm: N2-Formyl-N1-(5-phospho-D-ribosyl) glycinamide, FPRAm: 2-(Formamido)-N1-(5-phospho-D-ribosyl) acetamidine, AIR: 5-amino-1-(5-phospho-D-ribosyl)imidazole, 5AIZC: 5-amino-1-(5-phospho-D-ribosyl) imidazole-4-carboxylate, 25AICS: (S)-2-[5-Amino-1-(5-phospho-D-ribosyl) imidazole-4-carboxamido]succinate, AICar: 5-Amino-1-(5-Phospho-D-ribosyl)imidazole-4-carboxamide, FPRICa: 5-Formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide