Table 3

Gold standard set of essential enzymes

EC

Reaction

Choke-points

Found by FBA

Comment

Reference


1.1.1.205

IMP dehydrogenase

Yes

No

Precursor import (adenosine, hypoxanthine, inosine)

[133]

1.1.1.267

1-deoxy-D-xylulose-5-phosphate reducetoisomerase

Yes

Yes

[84]

1.3.1.9

enoyl-ACP-reductase

Yes

Yes

[134-136]

1.3.3.1

Dihydroorotate oxidase

No

Yes

[92-95,137]

1.3.99.1

Succinate dehydrogenase

No

No

Presumably unspecific off-target effects

[75]

1.5.1.3

Dihydrofolate reductase

No

No

Necessary to block all reactions catalyzed by the enzyme

[138-140]

1.6.5.3

NADH dehydrogenase (ubiquinone)

No

No

Presumably unspecific off-target effects

[74]

1.8.1.7

glutathione reductase

Yes

Yes

[141,142]

1.8.1.9

thioredoxin reductase

Yes

Yes

[143,144]

1.10.2.2

cytochrome c reductase

Yes

Yes

[145]

1.15.1.1

superoxide dismutase

Yes

Yes

[146]

1.17.4.1

Ribonucleoside-diphosphate reductase

No

Yes

[147-149]

2.1.1.100

Protein-S-isoprenylcysteine-O-methyltransferase

Yes

Yes

[150,151]

2.1.1.103

Phosphoethanolamine methyltrans-ferase

Yes

No

Presumably unspecific off-target effects

[77,79]

2.1.1.45

Thymidylate synthase

No

Yes

[152,153]

2.1.1.64

3-Demethylubiquinone-9,3-O-methyltransferase

Yes

Yes

[154]

2.3.1.24

sphingosine-N-acyltransferase

Yes

Yes

[155]

2.3.1.37

delta-aminolevulinate synthase

Yes

Yes

[99,101]

2.3.1.41

3-Oxoacyl-[acyl-carrier protein] synthase

Yes

Yes

[156,157]

2.3.1.50

serine-palmitoyl transferase

No

Yes

[155]

2.4.2.1

Purine-nucleoside phosphorylase

Yes

No

Precursor import (hypoxanthine, xanthine)

[158]

2.4.2.8

Hypoxanthine phosphoribosyltransferase

Yes

No

Necessary to block all reactions catalyzed by the enzyme

[159-161]

2.5.1.15

Dihydropteroate synthase

Yes

No

Precursor import (folate)

[162-164]

2.5.1.16

Spermidine synthase

Yes

No

Precursor import (spermidine)

[165]

2.5.1.18

Glutathione transferase

Yes

Yes

[166-169]

2.5.1.19

3-Phosphoshikimate 1- carboxyvinyltransferase

Yes

No

Precursor import (4-aminobenzoate, folate)

[170]

2.5.1.58

Farnesyl-diphosphate Farnesyltransferase

No

Yes

[171]

2.7.1.32

Choline kinase

No

No

Presumably unspecific off-target effects

[78]

2.7.8.3

Ceramide-cholinephosphotransferase

Yes

Yes

[155]

3.3.1.1

S-adenosyl-l-homocysteine hydrolase

Yes

Yes

[172-175]

3.4.11.1

leucine aminopeptidase

Yes

No

Precursor import (amino acids)

[176]

3.4.14.1

dipeptidyl aminopeptidase 1

No

No

Precursor import (amino acids)

[177]

3.4.23.38

plasmepsins (aspartic acid proteases)

No

No

Precursor import (amino acids)

[178,179]

3.4.23.39

plasmepsins (aspartic acid proteases)

No

No

Precursor import (amino acids)

[178,179]

3.5.1.89

N-acetyl glucosaminylphosphatidyli-nositol deacetylase

No

Yes

[180]

3.5.2.3

dihydroorotase

Yes

Yes

[96,137]

3.5.4.4

Adenosine deaminase

Yes

No

Precursor import (hypoxanthine, inosine, xanthine)

[181,182]

4.1.1.17

Ornithine decarboxylase

No

No

Precursor import (spermidine, putrescine); alternative reaction R01152

[183-185]

4.1.1.23

Orotidine-5'-phosphate decarboxylase

Yes

Yes

[89-91,97,98]

4.1.1.50

Adenosylmethionine decarboxylase

No

No

Precursor import (spermidine)

[186]

4.1.2.13

Fructose-bisphosphate aldolase

Yes

No

Presumable main antimalarial effect is impaired host cell invasion

[187,188]

4.2.1.1

carbonic anhydrase

Yes

Yes

[87]

4.2.1.24

Delta-aminolevulinic acid dehydratase

No

Yes

[100]

4.2.1.58-61

3-hydroxyacyl-ACP dehydratase

Yes

Yes

[189]

4.2.3.5

Chorismate synthase

Yes

No

Precursor import (4-aminobenzoate, folate)

[92]

4.4.1.5

Lactoylglutathione lyase

Yes

Yes

[190]

4.6.1.12

2-C-methyl-D-erythritol-2,4- Cyclodiphosphate-synthase

No

Yes

[86]

5.99.1.2

topoisomerase I

Yes

Yes

[191]

5.99.1.3

topoisomerase II

Yes

Yes

[192-194]

6.1.1.3

Threonine-tRNA ligase

Yes

Yes

[195]

6.1.1.7

Alanine-tRNA ligase

Yes

Yes

[196]

6.3.2.2

Gamma-glutamylcysteine synthetase

Yes

Yes

[144,197,198]

6.3.4.4

Adenylosuccinate synthetase

Yes

Yes

[199]

6.3.5.2

GMP synthetase

No

No

Necessary to block all reactions catalyzed by the enzyme; precursor import(guanine/guanosine)

[200]

6.3.5.5

Carbamoyl-phosphate synthase (glutamine-hydrolysing)

No

Yes

[88]

6.3.5.8

amino-deoxychorismate synthase

No

No

Precursor import (4-aminobenzoate, folate)

[128]

6.4.1.2

Acetyl-CoA carboxylase

Yes

Yes

[156]


Huthmacher et al. BMC Systems Biology 2010 4:120   doi:10.1186/1752-0509-4-120

Open Data