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Table 3 Essential enzymes and potential chemical inhibitors

From: Genome-scale reconstruction of the metabolic network in Staphylococcus aureus N315: an initial draft to the two-dimensional annotation

Enzyme name

Potential Inhibitor

Prior testing?

Reference

acetyl-CoA carboxylase

pseudopeptide pyrrolidine dione antibiotics

SA, B

[45]

4-amino-4-deoxychorismate synthase

(6s)-6-fluoroshikimate

B

[46]

Adenosylmethionine decarboxylase

CGP 40215A, AdoMao

B

[47, 48]

asparagine synthase (glutamine-hydrolysing)

mucochloric and mucobromic acids, L-cysteine sulfinic acid

B

[49, 50]

dihydrofolate reductase

methylpteridines

B

[51]

dihydropteroate synthase

Sulfone and sulfanilamide sulfa drugs

B

[52, 53]

3-dehydroquinate synthase

carbocyclic inhibitors

B

[54]

FMN adenylyltransferase (FAD synthase)

Riboflavin 5'-pyrophosphate

F

[55]

glycerol-3-phosphate dehydrogenase (NADP)

5-n-alk(en)ylresorcinols

NF

[56]

glutamine synthetase

L-methionine sulfoximine, aminomethylene-bisphosphonic acid derivatives

NF

[57, 58]

glutamyl-tRNA reductase

see table I in paper

NF

[59]

GTP cyclohydrolase I

Diamino-6-hydroxypyrimidine, pterins

NF

[60, 61]

Hydroxymethylglutaryl CoA reductase (ir)

statins

NF

[62, 63]

Hydroxymethylglutaryl CoA synthase (ir)

beta-lactone, 3-Hydroxy-3-methylglutaryldithio-coenzyme A

NF

[64, 65]

isopentenyl-diphosphate D-isomerase

NE21650

NF

[66]

methionine adenosyltransferase

adduncts 14 and 16

B

[67]

Phosphatidate phosphatase

Propranolol

NF

[68]

phosphoribosylpyrophosphate synthetase

MRPP, ARPP

NF

[69]

riboflavin synthase

9-D-ribitylamino-1,3,7,9-tetrahydro-2,6,8-purinetriones

B

[70]

spermidine synthase

adenosylspermidine, dicyclohexylamine

SA, B

[71, 72]

thiamine transport via ABC system

azidobenzoyl derivatives of thiamin, methylene blue

F

[73, 74]

thioredoxin reductase

Arsenicals, Aurothioglucose

NF

[75, 76]

UDP-N-acetylglucosamine 4-epimerase

uridine analogs

NF

[77]

UDP-N-acetylenolpyruvoylglucosamine reductase

4-thiazolidinones

B

[78]

  1. A reasonable number of enzymes that are computationally predicted to be essential for the growth of S. aureus have inhibitors. These molecules are potential drugs against this organism. The prior testing column uses abbreviations to indicate if we located evidence that the listed compounds had been tested in S. aureus (SA), other bacteria (B), fungi (F), or if no evidence was located (NF). The interested reader should consult the relevant references for full details regarding these potential inhibitors.