Skip to main content

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