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Table 4 Knockout predictions with experimental validation

From: Novel Plasmodium falciparum metabolic network reconstruction identifies shifts associated with clinical antimalarial resistance

Enzyme Gene In vitro In vitro method Species Citation iTH366 iPfal17
Dihydrofolate reductase; thymidylate synthase PFD0830w L Inhibitor (1843 U89) Pf [142] L L
FABI, enoyl-acyl carrier reductase PFF0730c 1) L
2) NL
1) Inhibitor (Triclosan)a 2) Gene KO; siRNA 1) Pf
2) Pb
1) [99]
2) [143, 144]
- NL
FABB/F 3-oxoacyl-acyl-carrier protein synthase I/II PFF1275c 1) L
2) NL
1) Inhibitor (Cerulenin)
2) Gene KO
1) Pf
2) Pb
1) [99]
2) [144]
- NL
Dihydroorotate dehydrogenase PFF0160c L RNAi; Inhibitors (several) Pf [145, 146] L L
Adenosine deaminase PF10_0289 L Inhibitor (methylthiocoformycin) Pf [102] Lb c cKO: NL
Deoxyuridine 5-triphosphate nucleotido- hydrolase PF11_0282 L Inhibitors (several) Pf [147] NL L
Lactoyl glutathione lyase PF11_0145 PFF0230c L Inhibitor (S-p-bromobenzylglutathione diethyl ester) Pf [148] NL NL
Sphingomyelinase PFL1870c L Inhibitor (Scyphostatin) Pf [149] NL NL (GR)
Plasmepsin II PF14_0077 L Inhibitors (several) Pf [150] - NL
Cytosolic lysyl-tRNA synthetase PF13_0262 L Inhibitor (cladosporin) Pf [151] - L
Gamma-Glutamylcysteine synthase PFI0925w 1) L
2) NL
1) Inhibitor (L-buthionine sulfoximine); fail to Gene KO
2) Gene KO
1) Pf
2) Pb
1) [152]
2) [27]
- NL
Glutathion s-transferase PF3D7_ 1419300 L Inhibitors (ellagic acid, others) Pf [153] - NL
Glutathione reductase PF3D7_ 1419800 1) L
2) NL
1) Inhibitors (several); fail to KO
2) Gene KO
1) Pf
2) Pb
1) [154, 155]
2) [156]
- NL
5-Aminolevulinic acid synthase PF3D7_ 1246100 1) NL
2) L
1) Gene KO
2) Inhibitor (Succinyl acetone)
1) Pf, Pb
2) Pf
1) [100, 101]
2) [99]
L NL
Aconitase PF13_0229 NL Gene KO; Inhibitor (Sodium fluoroacetate) Pf [60, 61] - NL
α-Ketoglutarate dehydrogenase PF3D7_ 0820700 NL Gene KO Pf [60] - NL
Succinyl-CoA synthetase PF3D7_ 1108500 NL Gene KO Pf [60] - NL
Protoporphyrinoxygen oxidase PF10_0275 L Inhibitor (Acifluorfen) Pf [99] L NL
  1. Predictions for 18 enzymes of interest are included here. See Additional file 3: Table S7 for the complete list of predictions
  2. Italics, inconsistent with experimental results; Bold, conflicting experimental results; Tg, Toxoplasma gondii; Pf, Plasmodium falciparum; Pb, Plasmodium berghei; a, known off target effects; b, modified media conditions; c, contrary to published; KO, knockout; cKO, conditional KO; GR, growth reducing; L, lethal; NL, nonlethal