Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
twitter

Escherichia coli K-12 substr. MG1655 Enzyme: enoyl-[acyl-carrier-protein] reductase



Gene: fabI Accession Numbers: EG11528 (EcoCyc), b1288, ECK1283

Synonyms: envM, gts, qmeA, enoyl-ACP reductase

Regulation Summary Diagram: ?

Subunit composition of enoyl-[acyl-carrier-protein] reductase = [FabI]4
         enoyl-[acyl-carrier-protein] reductase subunit = FabI

Summary:
The FabI protein is an enoyl-acyl carrier protein reductase (enoyl-ACP reductase) that catalyzes an essential step in fatty acid biosynthesis, the reduction of the 2,3-double bond in the elongating fatty acid moiety [Bergler96]. Enoyl-ACP reductase is inhibited by acyl-ACP, probably through product inhibition, thus regulating fatty acid synthesis at a significant point [Heath95].

FabI is the only enoyl-acyl carrier protein reductase in E. coli and is essential for growth [Heath95, Goh09]. The enzyme is also involved in the elongation of 3-ketoglutaryl-[acp]-methyl-ester to pimeloyl-[acp]-methyl-ester, part of the biotin biosynthesis pathway [Lin10].

The fabI gene (previously referred to as envM or qmeA) was identified, temperature-sensitive mutants were isolated, and its protein product was purified and characterized [Bergler92, Bergler94a, Bergler96, Kleerebezem96a].

Early work described two activities for enoyl-ACP reductase, one NADH-dependent and one NADPH-dependent, that catalyze the reduction of enoyl derivatives of carbon chain length from 4 to 16 [Weeks68]. The latter activity was B-specific with respect to NADPH [Saito80]. However, it was later shown that both activities reside in FabI [Bergler96]. The activity with NADH was over 17-fold higher than with NADPH [Bergler96], thus the designation of the E. coli enzyme as EC 1.3.1.9. The FabI protein was identified in E. coli by studying mutants resistant to diazaborines, which are antimicrobial agents that inhibit lipid synthesis [Turnowsky89].

FabI activity plays a determinant role in completing rounds of fatty acid elongation. In an in vitro fatty acid biosynthesis system using purified recombinant enzymes, FabI was shown to influence the equilibrium of the preceding reversible dehydratase-catalyzed reaction by pulling it in the direction of fatty acid elongation, thus demonstrating the necessity of FabI for fatty acid elongation [Heath95, Heath96a]. They also demonstrated a correction of the fatty acid synthesis defect in extracts of a fabI temperature-sensitive mutant by addition of purified FabI, which restored the NADH-dependent elongation of long chain saturated and unsaturated acyl-ACPs [Heath95].

A steady state kinetic analysis of an in vitro reconstituted E. coli fatty acid biosynthesis system was performed in which increased concentrations of FabI and FabZ were found to increase the turnover of fatty acid synthesis. Mass spectrometric analysis of the products showed that the most abundant ACP species were bound to chains of length C6, C10, C16 and C18 [Yu11].

FabI is the target of triclosan, a widely used antimicrobial compound [McMurry98, Heath99, Sivaraman03, Sivaraman04], although triclosan may have additional targets [Yu12]. FabI is also of great interest as a target for the development of other antimicrobial drugs [Levy01, Zhang04a, Ling04, Protasevich04, Rafi06a, Kitagawa07, Zheng07, Karioti08, Sampson09, Yao10, Escaich11].

Crystal structures have been determined for FabI in complex with NAD+ and diazaborine inhibitors [Baldock96], NAD+ and triclosan [Levy99, Qiu99, Ward99], NADH and triclosan [Stewart99], NAD+ and other inhibitors [Heerding01, Seefeld01, Miller02a, Seefeld03], and FabI mutants with NAD+ and triclosan [Singh11a]. The crystal structure of FabI co-crystallized with 2-dodecenoyl-ACP has been determined, and analyzed using molecular dynamics simulations and model building [Rafi06].

In crystallographic analyses FabI appeared to be a homotetramer [Baldock96, Ward99, Stewart99]. It was also determined to be a homotetramer by native gel electrophoresis [Protasevich04].

In fabI gene replacement studies, a component of the plant fatty acid synthase system was shown to functionally replace fabI in E. coli [Kater94]. FabI was also used in the development of a biarsenical-tetracysteine labeling system [Yang10].

In E. coli the enzymes of fatty acid biosynthesis are found in the soluble fraction of the cell, and the acyl carrier protein has been localized in the cytoplasm [Jackowski85].

Reviews: [Zhang04b, White05, Lu08, MassengoTiasse09, Chan10], and Cronan, J.E. Jr., and C.O. Rock (2008) "Biosynthesis of Membrane Lipids" EcoSal 3.6.4 [ECOSAL]

Locations [Comment 1]: cytosol, membrane

Map Position: [1,348,275 <- 1,349,063] (29.06 centisomes)
Length: 789 bp / 262 aa

Molecular Weight of Polypeptide: 27.864 kD (from nucleotide sequence)

pI: 5.88

Unification Links: ASAP:ABE-0004327 , CGSC:812 , DIP:DIP-31867N , EchoBASE:EB1490 , EcoGene:EG11528 , EcoliWiki:b1288 , Mint:MINT-1251203 , OU-Microarray:b1288 , PortEco:fabI , PR:PRO_000022565 , Pride:P0AEK4 , Protein Model Portal:P0AEK4 , RefSeq:NP_415804 , RegulonDB:EG11528 , SMR:P0AEK4 , String:511145.b1288 , Swiss-Model:P0AEK4 , UniProt:P0AEK4

Relationship Links: InterPro:IN-FAMILY:IPR002347 , InterPro:IN-FAMILY:IPR014358 , InterPro:IN-FAMILY:IPR016040 , PDB:Structure:1C14 , PDB:Structure:1D8A , PDB:Structure:1DFG , PDB:Structure:1DFH , PDB:Structure:1DFI , PDB:Structure:1I2Z , PDB:Structure:1I30 , PDB:Structure:1LX6 , PDB:Structure:1LXC , PDB:Structure:1MFP , PDB:Structure:1QG6 , PDB:Structure:1QSG , PDB:Structure:2FHS , PDB:Structure:3PJD , PDB:Structure:3PJE , PDB:Structure:3PJF , Pfam:IN-FAMILY:PF00106 , Prints:IN-FAMILY:PR00081

In Paralogous Gene Group: 272 (2 members)

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0008610 - lipid biosynthetic process Inferred from experiment [Turnowsky89, Bergler94a]
GO:0009102 - biotin biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA12, Lin10]
GO:0030497 - fatty acid elongation Inferred from experiment [Heath96a, Heath95]
GO:0051289 - protein homotetramerization Inferred from experiment [Stewart99]
GO:0006629 - lipid metabolic process Inferred by computational analysis [UniProtGOA11]
GO:0006631 - fatty acid metabolic process Inferred by computational analysis [UniProtGOA11]
GO:0006633 - fatty acid biosynthetic process Inferred by computational analysis [UniProtGOA12, UniProtGOA11, GOA01]
GO:0046677 - response to antibiotic Inferred by computational analysis [UniProtGOA11]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11, GOA01]
Molecular Function: GO:0004318 - enoyl-[acyl-carrier-protein] reductase (NADH) activity Inferred from experiment Inferred by computational analysis [GOA01a, GOA01, Bergler96, Bergler94a]
GO:0042802 - identical protein binding Inferred from experiment [Protasevich04]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005829 - cytosol Inferred from experiment [Ishihama08, LopezCampistrou05]
GO:0016020 - membrane Inferred from experiment [Lasserre06]
GO:0005737 - cytoplasm Inferred by curator

MultiFun Terms: metabolism biosynthesis of building blocks fatty acids and phosphatidic acid

Essentiality data for fabI knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox No 37 Aerobic 7   No [Baba06, Comment 2]

Credits:
Created 10-Apr-2013 by Fulcher C , SRI International
Last-Curated ? 11-Apr-2013 by Fulcher C , SRI International


Enzymatic reaction of: enoyl-[acyl-carrier-protein] reductase

EC Number: 1.3.1.9

an acyl-[acyl-carrier protein] + NAD+ <=> a trans-2-enoyl-[acyl-carrier protein] + NADH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.


Enzymatic reaction of: cis-vaccen-2-enoyl-[acp] reductase (enoyl-[acyl-carrier-protein] reductase)

EC Number: 1.3.1.9

a cis-vaccen-2-enoyl-[acp] + NADH + H+ <=> a cis-vaccenoyl-[acp] + NAD+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: superpathway of unsaturated fatty acids biosynthesis (E. coli) , cis-vaccenate biosynthesis

Summary:
A correction of the fatty acid synthesis defect in extracts of a fabI temperature-sensitive mutant was demonstrated. Addition of purified FabI restored the NADH-dependent elongation of long chain saturated and unsaturated acyl-ACPs [Heath95].


Enzymatic reaction of: 2,3,4-saturated fatty acyl-[acp]:NAD+ oxidoreductase (enoyl-[acyl-carrier-protein] reductase)

Synonyms: NADH-dependent enoyl-ACP reductase, enoyl-(acyl-carrier-protein)-reductase-(NADH), enoyl-ACP reductase, acyl-(ACP):NAD+ oxidoreductase, enoyl-ACP reductase (NADH)

EC Number: 1.3.1.9

a trans-2-enoyl-[acyl-carrier protein] + NADH + H+ <=> a 2,3,4-saturated fatty acyl-[acp] + NAD+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown. [Heath95]

Alternative Substrates for a trans-2-enoyl-[acyl-carrier protein]: a trans-2-enoyl-CoA [Weeks68 , Bergler94a ]

Alternative Substrates for NADH: NADPH [Bergler96 ]

In Pathways: superpathway of fatty acid biosynthesis I (E. coli) , fatty acid elongation -- saturated

Summary:
The activity with NADH was over 17-fold higher than with NADPH [Bergler96].

Activators (Unknown Mechanism): N-ethylmaleimide [Weeks68]

Inhibitors (Noncompetitive): a diazaborine [Bergler94a]

Inhibitors (Irreversible): triclosan [Heath99]

Inhibitors (Unknown Mechanism): an acyl-[acyl-carrier protein] [Heath95, Comment 3] , p-hydroxymercuribenzoate [Weeks68] , iodoacetate [Weeks68]

Primary Physiological Regulators of Enzyme Activity: an acyl-[acyl-carrier protein]


Enzymatic reaction of: cis5-dodecenoyl-[acp]:NAD+ oxidoreductase (enoyl-[acyl-carrier-protein] reductase)

EC Number: 1.3.1.9

a trans3-cis5-dodecenoyl-[acp] + NADH + H+ <=> a cis5-dodecenoyl-[acp] + NAD+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown. [Heath95]

In Pathways: superpathway of fatty acid biosynthesis I (E. coli) , superpathway of unsaturated fatty acids biosynthesis (E. coli) , cis-dodecenoyl biosynthesis


Enzymatic reaction of: palmitoleoyl-[acp]:NAD+ oxidoreductase (enoyl-[acyl-carrier-protein] reductase)

EC Number: 1.3.1.9

a trans3-cis9-hexadecenoyl-[acp] + NADH + H+ <=> a palmitoleoyl-[acp] + NAD+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown. [Heath95]

In Pathways: superpathway of unsaturated fatty acids biosynthesis (E. coli) , palmitoleate biosynthesis I


Enzymatic reaction of: cis7-tetradecenoyl-[acp]:NAD+ oxidoreductase (enoyl-[acyl-carrier-protein] reductase)

EC Number: 1.3.1.9

a trans3-cis7-tetradecenoyl-[acp] + NADH + H+ <=> a cis7-tetradecenoyl-[acp] + NAD+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown. [Heath95]

In Pathways: superpathway of unsaturated fatty acids biosynthesis (E. coli) , palmitoleate biosynthesis I


Enzymatic reaction of: enoylpimeloyl-[acp] methyl ester reductase (enoyl-[acyl-carrier-protein] reductase)

EC Number: 1.3.1.9

a pimeloyl-[acp] methyl ester + NAD+ <=> an enoylpimeloyl-[acp] methyl ester + NADH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.

In Pathways: biotin biosynthesis I , 8-amino-7-oxononanoate biosynthesis I


Enzymatic reaction of: enoylglutaryl-[acp] methyl ester reductase (enoyl-[acyl-carrier-protein] reductase)

EC Number: 1.3.1.9

a glutaryl-[acp] methyl ester + NAD+ <=> an enoylglutaryl-[acp] methyl ester + NADH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.

In Pathways: biotin biosynthesis I , 8-amino-7-oxononanoate biosynthesis I


Enzymatic reaction of: crotonyl-[acyl-carrier-protein] reductase (enoyl-[acyl-carrier-protein] reductase)

EC Number: 1.3.1.9

a crotonyl-[acp] + NADH + H+ <=> a butyryl-[acp] + NAD+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown. [Heath95]

In Pathways: palmitate biosynthesis II (bacteria and plants)

Summary:
Inhibition by palmitoyl-CoA has been demonstrated [Bergler96] but its physiological significance has been questioned due to the detergent properties of palmitoyl-CoA (see [ECOSAL] citation above).

Inhibitors (Unknown Mechanism): palmitoyl-CoA [Bergler96]

Kinetic Parameters:

Substrate
Km (μM)
Citations
a crotonyl-[acp]
22.0
[Bergler94a]


Enzymatic reaction of: hexanoyl-[acyl-carrier-protein] reductase (enoyl-[acyl-carrier-protein] reductase)

EC Number: 1.3.1.9

a trans hex-2-enoyl-[acp] + NADH + H+ <=> a hexanoyl-[acyl-carrier-protein] + NAD+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown. [Heath95]

In Pathways: palmitate biosynthesis II (bacteria and plants)


Enzymatic reaction of: octanoyl-[acyl-carrier-protein] reductase (enoyl-[acyl-carrier-protein] reductase)

EC Number: 1.3.1.9

a trans oct-2-enoyl-[acp] + NADH + H+ <=> an octanoyl-[acp] + NAD+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown. [Heath95]

In Pathways: palmitate biosynthesis II (bacteria and plants)

Summary:
Epigallocatechin gallate was a competitive inhibitor with respect to NADH. The substrate for the inhibiton assay was trans-2-octanoyl-N-acetylcysteamine [Zhang04a].

Inhibitors (Competitive): (-)-epigallocatechin 3-gallate [Zhang04a]


Enzymatic reaction of: decanoyl-[acyl-carrier-protein] reductase (enoyl-[acyl-carrier-protein] reductase)

EC Number: 1.3.1.9

a trans2-decenoyl-[acp] + NADH + H+ <=> a decanoyl-[acp] + NAD+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown. [Heath95]

In Pathways: palmitate biosynthesis II (bacteria and plants)


Enzymatic reaction of: dodecanoyl-[acyl-carrier-protein] reductase (enoyl-[acyl-carrier-protein] reductase)

EC Number: 1.3.1.9

a trans dodec-2-enoyl-[acp] + NADH + H+ <=> a dodecanoyl-[acp] + NAD+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown. [Heath95]

In Pathways: palmitate biosynthesis II (bacteria and plants)

Kinetic Parameters:

Substrate
Km (μM)
Citations
a trans dodec-2-enoyl-[acp]
3.3
[Rafi06]


Enzymatic reaction of: myristoyl-[acyl-carrier-protein] reductase (enoyl-[acyl-carrier-protein] reductase)

EC Number: 1.3.1.9

a trans tetradec-2-enoyl-[acp] + NADH + H+ <=> a myristoyl-[acp] + NAD+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown. [Heath95]

In Pathways: palmitate biosynthesis II (bacteria and plants)


Enzymatic reaction of: palmitoyl-[acyl-carrier-protein] reductase (enoyl-[acyl-carrier-protein] reductase)

EC Number: 1.3.1.9

a trans hexadecenoyl-[acp] + NADH + H+ <=> a palmitoyl-[acp] + NAD+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown. [Heath95]

In Pathways: palmitate biosynthesis II (bacteria and plants)


Sequence Features

Feature Class Location Citations Comment
Cleavage-of-Initial-Methionine 1
[Frutiger96, Bergler92, Link97, UniProt12]
UniProt: Removed.
Chain 2 -> 262
[UniProt09]
UniProt: Enoyl-[acyl-carrier-protein] reductase [NADH];
Amino-Acid-Sites-That-Bind 13
[UniProt11]
UniProt: NAD; via carbonyl oxygen.
Nucleotide-Phosphate-Binding-Region 19 -> 20
[UniProt11]
UniProt: NAD.
Amino-Acid-Sites-That-Bind 40
[UniProt11]
UniProt: NAD.
Nucleotide-Phosphate-Binding-Region 64 -> 65
[UniProt11]
UniProt: NAD.
Amino-Acid-Sites-That-Bind 92
[UniProt11]
UniProt: NAD; via carbonyl oxygen.
Mutagenesis-Variant 93
[McMurry98, Bergler92, UniProt11]
Alternate sequence: G → V; UniProt: Triclosan resistance.
Alternate sequence: G → S; UniProt: Diazaborine resistance.
Amino-Acid-Sites-That-Bind 95
[UniProt11]
UniProt: Substrate; via amide nitrogen and carbonyl oxygen.
Mutagenesis-Variant 146
[Rafi06, UniProt11]
Alternate sequence: Y → F; UniProt: Large impact on catalysis, with kcat and kcat/Km for DD-ACP decreasing by around 50-fold compared with wild-type.
Active-Site 146
[UniProt11]
UniProt: Proton acceptor; Non-Experimental Qualifier: by similarity.
Mutagenesis-Variant 156
[Rafi06, UniProt11]
Alternate sequence: Y → F; UniProt: No effect on substrate reduction.
Active-Site 156
[UniProt10]
UniProt: Proton acceptor; Non-Experimental Qualifier: by similarity;
Mutagenesis-Variant 159
[McMurry98, UniProt11]
Alternate sequence: M → T; UniProt: Triclosan resistance.
Amino-Acid-Sites-That-Bind 163
[UniProt11]
UniProt: NAD.
Nucleotide-Phosphate-Binding-Region 192 -> 196
[UniProt11]
UniProt: NAD.
Mutagenesis-Variant 201
[Rafi06, UniProt11]
Alternate sequence: K → E; UniProt: Little activity toward DD-CoA and DD-ACP.
Alternate sequence: K → A; UniProt: No effect on substrate reduction.
Amino-Acid-Site 201
[UniProt11]
UniProt: Involved in acyl-ACP binding; Sequence Annotation Type: site.
Mutagenesis-Variant 203
[McMurry98, UniProt11]
Alternate sequence: F → L; UniProt: Triclosan resistance.
Mutagenesis-Variant 204
[Rafi06, UniProt11]
Alternate sequence: R → E; UniProt: Causes a further reduction in kcat/Km for reduction of DD-ACP without affecting kcat/Km for the DD-CoA substrate.
Alternate sequence: R → A; UniProt: No effect on substrate reduction.
Amino-Acid-Site 204
[UniProt11]
UniProt: Involved in acyl-ACP binding; Sequence Annotation Type: site.
Mutagenesis-Variant 205
[Rafi06, UniProt11]
Alternate sequence: K → E; UniProt: Causes a further reduction in kcat/Km for reduction of DD-ACP without affecting kcat/Km for the DD-CoA substrate. Has a larger impact on substrate reduction.
Alternate sequence: K → A; UniProt: No effect on substrate reduction.
Amino-Acid-Site 205
[UniProt11]
UniProt: Involved in acyl-ACP binding; Sequence Annotation Type: site.
Mutagenesis-Variant 241
[UniProt10a]
Alternate sequence: S → F; UniProt: Produces temperature-sensitive phenotype;


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
3/2/1998 (pkarp) Merged genes G482/b1288 and EG11528/fabI
10/20/97 Gene b1288 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11528; confirmed by SwissProt match.


References

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Baldock96: Baldock C, Rafferty JB, Sedelnikova SE, Baker PJ, Stuitje AR, Slabas AR, Hawkes TR, Rice DW (1996). "A mechanism of drug action revealed by structural studies of enoyl reductase." Science 274(5295);2107-10. PMID: 8953047

Bergler92: Bergler H, Hogenauer G, Turnowsky F (1992). "Sequences of the envM gene and of two mutated alleles in Escherichia coli." J Gen Microbiol 1992;138 ( Pt 10);2093-100. PMID: 1364817

Bergler94a: Bergler H, Wallner P, Ebeling A, Leitinger B, Fuchsbichler S, Aschauer H, Kollenz G, Hogenauer G, Turnowsky F (1994). "Protein EnvM is the NADH-dependent enoyl-ACP reductase (FabI) of Escherichia coli." J Biol Chem 1994;269(8);5493-6. PMID: 8119879

Bergler96: Bergler H, Fuchsbichler S, Hogenauer G, Turnowsky F (1996). "The enoyl-[acyl-carrier-protein] reductase (FabI) of Escherichia coli, which catalyzes a key regulatory step in fatty acid biosynthesis, accepts NADH and NADPH as cofactors and is inhibited by palmitoyl-CoA." Eur J Biochem 242(3);689-94. PMID: 9022698

Chan10: Chan DI, Vogel HJ (2010). "Current understanding of fatty acid biosynthesis and the acyl carrier protein." Biochem J 430(1);1-19. PMID: 20662770

ECOSAL: "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

Escaich11: Escaich S, Prouvensier L, Saccomani M, Durant L, Oxoby M, Gerusz V, Moreau F, Vongsouthi V, Maher K, Morrissey I, Soulama-Mouze C (2011). "The MUT056399 inhibitor of FabI is a new antistaphylococcal compound." Antimicrob Agents Chemother 55(10);4692-7. PMID: 21825292

Frutiger96: Frutiger S., Hughes G.J., Pasquali C., Hochstrasser D.F. (1996). Data submission to UniProtKB on 1996-02.

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

Goh09: Goh S, Boberek JM, Nakashima N, Stach J, Good L (2009). "Concurrent growth rate and transcript analyses reveal essential gene stringency in Escherichia coli." PLoS One 4(6);e6061. PMID: 19557168

Heath95: Heath RJ, Rock CO (1995). "Enoyl-acyl carrier protein reductase (fabI) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli." J Biol Chem 270(44);26538-42. PMID: 7592873

Heath96a: Heath RJ, Rock CO (1996). "Regulation of fatty acid elongation and initiation by acyl-acyl carrier protein in Escherichia coli." J Biol Chem 1996;271(4);1833-6. PMID: 8567624

Heath99: Heath RJ, Rubin JR, Holland DR, Zhang E, Snow ME, Rock CO (1999). "Mechanism of triclosan inhibition of bacterial fatty acid synthesis." J Biol Chem 1999;274(16);11110-4. PMID: 10196195

Heerding01: Heerding DA, Chan G, DeWolf WE, Fosberry AP, Janson CA, Jaworski DD, McManus E, Miller WH, Moore TD, Payne DJ, Qiu X, Rittenhouse SF, Slater-Radosti C, Smith W, Takata DT, Vaidya KS, Yuan CC, Huffman WF (2001). "1,4-Disubstituted imidazoles are potential antibacterial agents functioning as inhibitors of enoyl acyl carrier protein reductase (FabI)." Bioorg Med Chem Lett 11(16);2061-5. PMID: 11514139

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Jackowski85: Jackowski S, Edwards HH, Davis D, Rock CO (1985). "Localization of acyl carrier protein in Escherichia coli." J Bacteriol 162(1);5-8. PMID: 3884600

Karioti08: Karioti A, Skaltsa H, Zhang X, Tonge PJ, Perozzo R, Kaiser M, Franzblau SG, Tasdemir D (2008). "Inhibiting enoyl-ACP reductase (FabI) across pathogenic microorganisms by linear sesquiterpene lactones from Anthemis auriculata." Phytomedicine 15(12);1125-9. PMID: 18424102

Kater94: Kater MM, Koningstein GM, Nijkamp HJ, Stuitje AR (1994). "The use of a hybrid genetic system to study the functional relationship between prokaryotic and plant multi-enzyme fatty acid synthetase complexes." Plant Mol Biol 25(5);771-90. PMID: 8075395

Kitagawa07: Kitagawa H, Kumura K, Takahata S, Iida M, Atsumi K (2007). "4-Pyridone derivatives as new inhibitors of bacterial enoyl-ACP reductase FabI." Bioorg Med Chem 15(2);1106-16. PMID: 17095231

Kleerebezem96a: Kleerebezem M, Heutink M, de Cock H, Tommassen J (1996). "The qmeA (ts) mutation of Escherichia coli is localized in the fabI gene, which encodes enoyl-ACP reductase." Res Microbiol 147(8);609-13. PMID: 9157486

Lasserre06: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726

Levy01: Levy CW, Baldock C, Wallace AJ, Sedelnikova S, Viner RC, Clough JM, Stuitje AR, Slabas AR, Rice DW, Rafferty JB (2001). "A study of the structure-activity relationship for diazaborine inhibition of Escherichia coli enoyl-ACP reductase." J Mol Biol 309(1);171-80. PMID: 11491286

Levy99: Levy CW, Roujeinikova A, Sedelnikova S, Baker PJ, Stuitje AR, Slabas AR, Rice DW, Rafferty JB (1999). "Molecular basis of triclosan activity." Nature 398(6726);383-4. PMID: 10201369

Lin10: Lin S, Hanson RE, Cronan JE (2010). "Biotin synthesis begins by hijacking the fatty acid synthetic pathway." Nat Chem Biol 6(9);682-8. PMID: 20693992

Ling04: Ling LL, Xian J, Ali S, Geng B, Fan J, Mills DM, Arvanites AC, Orgueira H, Ashwell MA, Carmel G, Xiang Y, Moir DT (2004). "Identification and characterization of inhibitors of bacterial enoyl-acyl carrier protein reductase." Antimicrob Agents Chemother 48(5);1541-7. PMID: 15105103

Link97: Link AJ, Robison K, Church GM (1997). "Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12." Electrophoresis 18(8);1259-313. PMID: 9298646

LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532

Lu08: Lu H, Tonge PJ (2008). "Inhibitors of FabI, an enzyme drug target in the bacterial fatty acid biosynthesis pathway." Acc Chem Res 41(1);11-20. PMID: 18193820

MassengoTiasse09: Massengo-Tiasse RP, Cronan JE (2009). "Diversity in enoyl-acyl carrier protein reductases." Cell Mol Life Sci 66(9);1507-17. PMID: 19151923

McMurry98: McMurry LM, Oethinger M, Levy SB (1998). "Triclosan targets lipid synthesis." Nature 394(6693);531-2. PMID: 9707111

Miller02a: Miller WH, Seefeld MA, Newlander KA, Uzinskas IN, Burgess WJ, Heerding DA, Yuan CC, Head MS, Payne DJ, Rittenhouse SF, Moore TD, Pearson SC, Berry V, DeWolf WE, Keller PM, Polizzi BJ, Qiu X, Janson CA, Huffman WF (2002). "Discovery of aminopyridine-based inhibitors of bacterial enoyl-ACP reductase (FabI)." J Med Chem 45(15);3246-56. PMID: 12109908

Protasevich04: Protasevich II, Brouillette CG, Snow ME, Dunham S, Rubin JR, Gogliotti R, Siegel K (2004). "Role of inhibitor aliphatic chain in the thermodynamics of inhibitor binding to Escherichia coli enoyl-ACP reductase and the Phe203Leu mutant: a proposed mechanism for drug resistance." Biochemistry 43(42);13380-9. PMID: 15491144

Qiu99: Qiu X, Janson CA, Court RI, Smyth MG, Payne DJ, Abdel-Meguid SS (1999). "Molecular basis for triclosan activity involves a flipping loop in the active site." Protein Sci 8(11);2529-32. PMID: 10595560

Rafi06: Rafi S, Novichenok P, Kolappan S, Zhang X, Stratton CF, Rawat R, Kisker C, Simmerling C, Tonge PJ (2006). "Structure of acyl carrier protein bound to FabI, the FASII enoyl reductase from Escherichia coli." J Biol Chem 281(51);39285-93. PMID: 17012233

Rafi06a: Rafi SB, Cui G, Song K, Cheng X, Tonge PJ, Simmerling C (2006). "Insight through molecular mechanics Poisson-Boltzmann surface area calculations into the binding affinity of triclosan and three analogues for FabI, the E. coli enoyl reductase." J Med Chem 49(15);4574-80. PMID: 16854062

Saito80: Saito K, Kawaguchi A, Okuda S, Seyama Y, Yamakawa T (1980). "Incorporation of hydrogen atoms from deuterated water and stereospecifically deuterium-labeled nicotin amide nucleotides into fatty acids with the Escherichia coli fatty acid synthetase system." Biochim Biophys Acta 618(2);202-13. PMID: 6990992

Sampson09: Sampson PB, Picard C, Handerson S, McGrath TE, Domagala M, Leeson A, Romanov V, Awrey DE, Thambipillai D, Bardouniotis E, Kaplan N, Berman JM, Pauls HW (2009). "Spiro-naphthyridinone piperidines as inhibitors of S. aureus and E. coli enoyl-ACP reductase (FabI)." Bioorg Med Chem Lett 19(18);5355-8. PMID: 19682901

Seefeld01: Seefeld MA, Miller WH, Newlander KA, Burgess WJ, Payne DJ, Rittenhouse SF, Moore TD, DeWolf WE, Keller PM, Qiu X, Janson CA, Vaidya K, Fosberry AP, Smyth MG, Jaworski DD, Slater-Radosti C, Huffman WF (2001). "Inhibitors of bacterial enoyl acyl carrier protein reductase (FabI): 2,9-disubstituted 1,2,3,4-tetrahydropyrido[3,4-b]indoles as potential antibacterial agents." Bioorg Med Chem Lett 11(17);2241-4. PMID: 11527706

Seefeld03: Seefeld MA, Miller WH, Newlander KA, Burgess WJ, DeWolf WE, Elkins PA, Head MS, Jakas DR, Janson CA, Keller PM, Manley PJ, Moore TD, Payne DJ, Pearson S, Polizzi BJ, Qiu X, Rittenhouse SF, Uzinskas IN, Wallis NG, Huffman WF (2003). "Indole naphthyridinones as inhibitors of bacterial enoyl-ACP reductases FabI and FabK." J Med Chem 46(9);1627-35. PMID: 12699381

Singh11a: Singh NJ, Shin D, Lee HM, Kim HT, Chang HJ, Cho JM, Kim KS, Ro S (2011). "Structural basis of triclosan resistance." J Struct Biol 174(1);173-9. PMID: 21094257

Sivaraman03: Sivaraman S, Zwahlen J, Bell AF, Hedstrom L, Tonge PJ (2003). "Structure-activity studies of the inhibition of FabI, the enoyl reductase from Escherichia coli, by triclosan: kinetic analysis of mutant FabIs." Biochemistry 42(15);4406-13. PMID: 12693936

Sivaraman04: Sivaraman S, Sullivan TJ, Johnson F, Novichenok P, Cui G, Simmerling C, Tonge PJ (2004). "Inhibition of the bacterial enoyl reductase FabI by triclosan: a structure-reactivity analysis of FabI inhibition by triclosan analogues." J Med Chem 47(3);509-18. PMID: 14736233

Stewart99: Stewart MJ, Parikh S, Xiao G, Tonge PJ, Kisker C (1999). "Structural basis and mechanism of enoyl reductase inhibition by triclosan." J Mol Biol 290(4);859-65. PMID: 10398587

Turnowsky89: Turnowsky F, Fuchs K, Jeschek C, Hogenauer G (1989). "envM genes of Salmonella typhimurium and Escherichia coli." J Bacteriol 171(12);6555-65. PMID: 2687243

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProt12: UniProt Consortium (2012). "UniProt version 2012-02 released on 2012-02-29 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."

Ward99: Ward WH, Holdgate GA, Rowsell S, McLean EG, Pauptit RA, Clayton E, Nichols WW, Colls JG, Minshull CA, Jude DA, Mistry A, Timms D, Camble R, Hales NJ, Britton CJ, Taylor IW (1999). "Kinetic and structural characteristics of the inhibition of enoyl (acyl carrier protein) reductase by triclosan." Biochemistry 38(38);12514-25. PMID: 10493822

Weeks68: Weeks G, Wakil SJ (1968). "Studies on the mechanism of fatty acid synthesis. 18. Preparation and general properties of the enoyl acyl carrier protein reductases from Escherichia coli." J Biol Chem 1968;243(6);1180-9. PMID: 4384650

White05: White SW, Zheng J, Zhang YM, Rock (2005). "The structural biology of type II fatty acid biosynthesis." Annu Rev Biochem 74;791-831. PMID: 15952903

Yang10: Yang H, He J, Hu F, Zheng C, Yu Z (2010). "Detection of Escherichia coli enoyl-ACP reductase using biarsenical-tetracysteine motif." Bioconjug Chem 21(7);1341-8. PMID: 20583783

Yao10: Yao J, Zhang Q, Min J, He J, Yu Z (2010). "Novel enoyl-ACP reductase (FabI) potential inhibitors of Escherichia coli from Chinese medicine monomers." Bioorg Med Chem Lett 20(1);56-9. PMID: 19959361

Yu11: Yu X, Liu T, Zhu F, Khosla C (2011). "In vitro reconstitution and steady-state analysis of the fatty acid synthase from Escherichia coli." Proc Natl Acad Sci U S A 108(46);18643-8. PMID: 22042840

Yu12: Yu BJ, Kim JA, Ju HM, Choi SK, Hwang SJ, Park S, Kim E, Pan JG (2012). "Genome-wide enrichment screening reveals multiple targets and resistance genes for triclosan in Escherichia coli." J Microbiol 50(5);785-91. PMID: 23124746

Zhang04a: Zhang YM, Rock CO (2004). "Evaluation of epigallocatechin gallate and related plant polyphenols as inhibitors of the FabG and FabI reductases of bacterial type II fatty-acid synthase." J Biol Chem 279(30);30994-1001. PMID: 15133034

Zhang04b: Zhang YM, Lu YJ, Rock CO (2004). "The reductase steps of the type II fatty acid synthase as antimicrobial targets." Lipids 39(11);1055-60. PMID: 15726819

Zheng07: Zheng CJ, Sohn MJ, Lee S, Hong YS, Kwak JH, Kim WG (2007). "Cephalochromin, a FabI-directed antibacterial of microbial origin." Biochem Biophys Res Commun 362(4);1107-12. PMID: 17825252

Other References Related to Gene Regulation

MendozaVargas09: Mendoza-Vargas A, Olvera L, Olvera M, Grande R, Vega-Alvarado L, Taboada B, Jimenez-Jacinto V, Salgado H, Juarez K, Contreras-Moreira B, Huerta AM, Collado-Vides J, Morett E (2009). "Genome-wide identification of transcription start sites, promoters and transcription factor binding sites in E. coli." PLoS One 4(10);e7526. PMID: 19838305


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Sun Nov 23, 2014, biocyc14.