Table 2. Bottleneck metabolites and affected reactions that determine the essential function of eight genes in iPfa.
| Essential Gene (E.C.) | Min. set of bottleneck metabolites | Reaction impacted after integration of the bottleneck metabolites concentration ranges1 (Reaction directionalities2) | All bottleneck metabolites among alternatives | Data set description |
|---|---|---|---|---|
| PF3D7_1415700 (2.3.1.50) | (i) CTP[r], Ethanolamine[c] | (Table SIII A and Table SIII D in S1 Methods) | CTP[r], Ethanolamine[c], Ethanolamine[r] | Required lower bound of 0.1 μM |
| (i) CTP[r], Ethanolamine[r] | ||||
| PF3D7_0111500 (2.7.4.-) | (i) UDP-N-acetyl-D-glucosamine[c], UTP[c], UDP-glucose[c], UDP-D-galactose[c] | (Table SIII B and Table SIII D in S1 Methods) | UDP-N-acetyl-D-glucosamine[c], UTP[c], UDP-glucose[c], UDP-D-galactose[c] | Required lower bound of 1 nM |
| PF3D7_0928900 (2.7.4.8) | (i) GTP[c] | (Table SIII C and Table SIII D in S1 Methods) | Diphosphate[c], GTP[c], 2,5-Diaminopyrimidine nucleoside triphosphate[c], GDP-mannose[c] | Required lower bound of 1 fM |
| (ii) 2,5-Diaminopyrimidine nucleoside triphosphate[c] | ||||
| PF3D7_0927900 (4.1.1.65) | (i) CDP[r], CDP-ethanolamine[r], Ethanolamine phosphate[r] | R02057_r (B) | CDP[r], CDP-ethanolamine[r], Ethanolamine phosphate[r] | MS 2012 [21] |
| R01468_r (B) | ||||
| R02038_r (B) | ||||
| T_c_to_r_C00189 (B) | ||||
| R02055_r (F) | ||||
| T_c_to_r_C00065 (F) | ||||
| T_c_to_r_C00011 (R) | ||||
| PF3D7_1351600 (2.7.1.30) | (i) CMP[r], Choline[r], AMP[r], ADP[r] | R01021_r (F) | CMP[r], Choline[r], AMP[r], CTP[r], ADP[r], ATP[r] | MS 2012 [21], NMR 2009 [19], NMR 2014 only strains 3D7, 7G8, C2(GC03), C4(Dd2), C6(7G8) [20] |
| R01890_r (F) | ||||
| R01321_r (F) | ||||
| (ii) CMP[r], Choline[r], AMP[r], ATP[r] | R01280_r (F) | |||
| R00127_r (F) | ||||
| R00094_r (F) | ||||
| (iii) CMP[r], Choline[r], AMP[r], CTP[r] | T_c_to_e_C00116 (F) | |||
| T_c_to_r_C00111 (F) | ||||
| R00842_r (R) | ||||
| (iv) CMP[r], Choline[r], CTP[r], ADP[r] | R00847_r (R) | |||
| T_c_to_r_C00013 (R) | ||||
| T_c_to_r_C00116 (R) | ||||
| PF3D7_1419800.1 (1.8.1.7) | (i) AMP[r], ATP[r] | R00094_r (F) | ADP[r], AMP[r], CDP-choline[c], ATP[r], CTP[r], CTP[c], CMP[r] | All the data [19–21] |
| R01280_r (F) | ||||
| PF3D7_0923800.2 (1.8.1.7) | R00127_r (F) | |||
| T_c_to_r_C00111 (F) | ||||
| PF3D7_1216200 (1.1.1.21) | R00842_r (R) | |||
| T_c_to_r_C00013 (R) |
1Reaction names as defined in iPfa. Metabolic reactions are defined with their R-5 digit identifier as obtained from the KEGG database. Transport reactions are marked with T_. Cellular compartments are defined with the reaction name: _r, endoplasmic reticulum; _c, cytosol; _e, extracellular (outside the parasite's cell).
2Reaction directionalities obtained with Thermodynamic Variability Analysis (TVA): (B) blocked, (F) forwards, (R) reverse. See the S4 Table for the reaction description.