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Escherichia coli K-12 substr. MG1655 Enzyme: 3-hydroxy-acyl-[acyl-carrier-protein] dehydratase



Gene: fabZ Accession Numbers: EG11284 (EcoCyc), b0180, ECK0179

Synonyms: sfhC21, sabA1, sefA, yaeA, (3R)-hydroxymyristoyl-ACP dehydratase, (3R)-hydroxymyristoyl-(acyl-carrier-protein) dehydratase

Regulation Summary Diagram: ?

Subunit composition of 3-hydroxy-acyl-[acyl-carrier-protein] dehydratase = [FabZ]6

Summary:
There are two β-hydroxyacyl-ACP dehydratases in E. coli, coded for by the fabA and fabZ genes. They both function in the dissociated or type II fatty acid synthase systems. The FabZ enzyme has a very broad substrate specificity. It catalyzes the dehydration of short chain β-hydroxyacyl-ACPs and long chain saturated and unsaturated β-hydroxyacyl-ACPs. While the FabA enzyme is most active on intermediate chain lengths, the two dehydratases do possess broad overlapping substrate specificities.

It is thought that the FabZ enzyme is the primary dehydratase involved in the unsaturated branch of the fatty acid synthesis pathway [Heath96b].

Certain mutations in fabZ have been found as suppressor mutations; its sabA1 allele changes the suppression of the OmpF315 phenotype by asmB1, and increased fabZ expression suppresses OmpF315 itself [Kloser98]. The sfhC21 allele of fabZ allows survival of ftsH null mutants [Ogura99].

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].

Gel electrophoresis data suggested that the FabZ protein undergoes oligomerization, although the precise subunit structure was not determined [Mohan94]. However, a later paper describing the crystal structure of Pseudomonas aeruginosa FabZ also included the determination of the subunit structure of E. coli His-tagged FabZ. The native apparent molecular mass of the E. coli enzyme determined by gel filtration chromatography was 112 kDa and the subunit apparent molecular mass determined by SDS-PAGE was 19 kDa, suggesting a hexamer ([Kimber04] see Fig. 3).

A steady state kinetic analysis of an in vitro reconstituted fatty acid biosynthesis system was performed in which increased concentrations FabZ and FabI were found to increase the turnover of fatty acid synthesis [Yu11].

fabZ mutants were isolated that were resistant to an antibiotic inhibitor of UDP-3-O-acyl-N-acetylglucosamine deacetylase encoded by lpxC. The mutants showed reduced enzymatic activity in vitro using 3-hydroxymyristoyl-ACP as substrate. In addition, a decreased level of LpxC was observed. This suggested that FabZ and LpxC activities are co-regulated and that the biosynthesis of fatty acids and lipid A is tightly regulated to maintain a balance between them [Zeng13]. These conclusions were supported by studies of an E. coli strain encoding a hyperactive FabZ enzyme [Schakermann13].

Improved production of long-chain fatty acids for biofuel in E. coli K-12 MG1655 was achieved by overexpressing the fabZ along with other genes of the elongation cycle [Jeon12, Lee13a, Jung13]. The important role of FabZ in producing unsaturated fatty acids was confirmed [Jung13].

Gene Citations: [Rhodius05, Dartigalongue01, Crowell86, Crowell87, Tomasiewicz87, Coleman88]

Locations: cytosol

Map Position: [202,101 -> 202,556] (4.36 centisomes)
Length: 456 bp / 151 aa

Molecular Weight of Polypeptide: 17.033 kD (from nucleotide sequence), 17 kD (experimental) [Mohan94 ]

Molecular Weight of Multimer: 116 kD (experimental) [Mohan94]

Isozyme Sequence Similarity:
FabA: YES

Unification Links: ASAP:ABE-0000613 , CGSC:30597 , DIP:DIP-31868N , EchoBASE:EB1261 , EcoGene:EG11284 , EcoliWiki:b0180 , Mint:MINT-1218564 , ModBase:P0A6Q6 , OU-Microarray:b0180 , PortEco:fabZ , PR:PRO_000022567 , Pride:P0A6Q6 , Protein Model Portal:P0A6Q6 , RefSeq:NP_414722 , RegulonDB:EG11284 , SMR:P0A6Q6 , String:511145.b0180 , Swiss-Model:P0A6Q6 , UniProt:P0A6Q6

Relationship Links: InterPro:IN-FAMILY:IPR010084 , InterPro:IN-FAMILY:IPR013114 , Pfam:IN-FAMILY:PF07977

In Paralogous Gene Group: 60 (2 members)

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0006633 - fatty acid biosynthetic process Inferred from experiment Inferred by computational analysis [GOA06, GOA01, Heath96b]
GO:0006629 - lipid metabolic process Inferred by computational analysis [UniProtGOA11]
GO:0009245 - lipid A biosynthetic process Inferred by computational analysis [UniProtGOA11, GOA06]
Molecular Function: GO:0008693 - 3-hydroxydecanoyl-[acyl-carrier-protein] dehydratase activity Inferred from experiment [Heath96b]
GO:0042802 - identical protein binding Inferred from experiment [Mohan94]
GO:0047451 - 3-hydroxyoctanoyl-[acyl-carrier-protein] dehydratase activity Inferred from experiment Inferred by computational analysis [GOA01a, Heath96b]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11]
GO:0016836 - hydro-lyase activity Inferred by computational analysis [GOA06, GOA01]
Cellular Component: GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, GOA06, GOA01]
GO:0005829 - cytosol

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

Essentiality data for fabZ knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox No 37 Aerobic 7   No [Baba06, Comment 1]

Credits:
Last-Curated ? 05-Apr-2013 by Fulcher C , SRI International


Enzymatic reaction of: 3-hydroxyglutaryl-[acp] methyl ester dehydratase (3-hydroxy-acyl-[acyl-carrier-protein] dehydratase)

EC Number: 4.2.1.59

a 3R-hydroxyglutaryl-[acp] methyl ester <=> an enoylglutaryl-[acp] methyl ester + H2O

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


Enzymatic reaction of: 3-hydroxypimeloyl-[acp] methyl ester dehydratase (3-hydroxy-acyl-[acyl-carrier-protein] dehydratase)

EC Number: 4.2.1.59

a 3R-hydroxypimeloyl-[acp] methyl ester <=> an enoylpimeloyl-[acp] methyl ester + H2O

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


Enzymatic reaction of: 3-hydroxy cis Δ7-tetradecenoyl-[acp] dehydratase (3-hydroxy-acyl-[acyl-carrier-protein] dehydratase)

EC Number: 4.2.1.59

a 3R-hydroxy cis Δ7-tetradecenoyl-[acp] <=> a trans3-cis7-tetradecenoyl-[acp] + H2O

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) , palmitoleate biosynthesis I


Enzymatic reaction of: 3-hydroxy cis Δ9-hexadecenoyl-[acp] dehydratase (3-hydroxy-acyl-[acyl-carrier-protein] dehydratase)

EC Number: 4.2.1.59

a 3R-hydroxy cis Δ9-hexadecenoyl-[acp] <=> a trans3-cis9-hexadecenoyl-[acp] + H2O

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) , palmitoleate biosynthesis I


Enzymatic reaction of: 3-hydroxy cis Δ5-dodecenoyl-[acp] dehydratase (3-hydroxy-acyl-[acyl-carrier-protein] dehydratase)

EC Number: 4.2.1.59

a 3R-hydroxy cis Δ5-dodecenoyl-[acp] <=> a trans3-cis5-dodecenoyl-[acp] + H2O

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


Enzymatic reaction of: (3R)-3-hydroxyacyl-[acyl-carrier protein] dehydratase (3-hydroxy-acyl-[acyl-carrier-protein] dehydratase)

EC Number: 4.2.1.59

a (3R)-3-hydroxyacyl-[acyl-carrier protein] <=> a trans-2-enoyl-[acyl-carrier protein] + H2O

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.

Alternative Substrates [Comment 2]:

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

Summary:
The reaction was shown to be reversible in an in vitro fatty acid biosynthesis system, but addition of FabI favored completion of the fatty acid elongation cycle [Heath95] (see pathway fatty acid elongation -- saturated).


Sequence Features

Feature Class Location Citations Comment
Active-Site 54
[UniProt10a]
UniProt: Non-Experimental Qualifier: by similarity;
Mutagenesis-Variant 85
[Ogura99, UniProt11]
Alternate sequence: L → P; UniProt: In sfhC21; suppresses an ftsH deletion mutant as well as an ftsH temperature-sensitive mutation. Probably stabilizes the enzyme.


Gene Local Context (not to scale): ?

Transcription Units:

Notes:

History:
3/2/1998 (pkarp) Merged genes G465/b0180 and EG11284/fabZ
10/20/97 Gene b0180 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11284; 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

Coleman88: Coleman J, Raetz CR (1988). "First committed step of lipid A biosynthesis in Escherichia coli: sequence of the lpxA gene." J Bacteriol 170(3);1268-74. PMID: 3277952

Crowell86: Crowell DN, Anderson MS, Raetz CR (1986). "Molecular cloning of the genes for lipid A disaccharide synthase and UDP-N-acetylglucosamine acyltransferase in Escherichia coli." J Bacteriol 168(1);152-9. PMID: 3531165

Crowell87: Crowell DN, Reznikoff WS, Raetz CR (1987). "Nucleotide sequence of the Escherichia coli gene for lipid A disaccharide synthase." J Bacteriol 1987;169(12);5727-34. PMID: 2824445

Dartigalongue01: Dartigalongue C, Missiakas D, Raina S (2001). "Characterization of the Escherichia coli sigma E regulon." J Biol Chem 276(24);20866-75. PMID: 11274153

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.

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

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

Heath96b: Heath RJ, Rock CO (1996). "Roles of the FabA and FabZ beta-hydroxyacyl-acyl carrier protein dehydratases in Escherichia coli fatty acid biosynthesis." J Biol Chem 1996;271(44);27795-801. PMID: 8910376

Jeon12: Jeon E, Lee S, Han SO, Yoon YJ, Lee J (2012). "Improved production of long-chain fatty acid in Escherichia coli by an engineering elongation cycle during fatty acid synthesis (FAS) through genetic manipulation." J Microbiol Biotechnol 22(7);990-9. PMID: 22580319

Jung13: Jung Y, Lee S, Lee J (2013). "Correlations Between FAS Elongation Cycle Genes Expression and Fatty Acid Production for Improvement of Long-Chain Fatty Acids in Escherichia coli." Appl Biochem Biotechnol 169(5);1606-19. PMID: 23322253

Kimber04: Kimber MS, Martin F, Lu Y, Houston S, Vedadi M, Dharamsi A, Fiebig KM, Schmid M, Rock CO (2004). "The structure of (3R)-hydroxyacyl-acyl carrier protein dehydratase (FabZ) from Pseudomonas aeruginosa." J Biol Chem 279(50);52593-602. PMID: 15371447

Kloser98: Kloser A, Laird M, Deng M, Misra R (1998). "Modulations in lipid A and phospholipid biosynthesis pathways influence outer membrane protein assembly in Escherichia coli K-12." Mol Microbiol 27(5);1003-8. PMID: 9535089

Lee13a: Lee S, Yoon YJ, Lee J (2013). "Enhancement of long-chain fatty acid production in Escherichia coli by coexpressing genes, including fabF, involved in the elongation cycle of fatty acid biosynthesis." Appl Biochem Biotechnol 169(2);462-76. PMID: 23225020

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

Mohan94: Mohan S, Kelly TM, Eveland SS, Raetz CR, Anderson MS (1994). "An Escherichia coli gene (FabZ) encoding (3R)-hydroxymyristoyl acyl carrier protein dehydrase. Relation to fabA and suppression of mutations in lipid A biosynthesis." J Biol Chem 1994;269(52);32896-903. PMID: 7806516

Ogura99: Ogura T, Inoue K, Tatsuta T, Suzaki T, Karata K, Young K, Su LH, Fierke CA, Jackman JE, Raetz CR, Coleman J, Tomoyasu T, Matsuzawa H (1999). "Balanced biosynthesis of major membrane components through regulated degradation of the committed enzyme of lipid A biosynthesis by the AAA protease FtsH (HflB) in Escherichia coli." Mol Microbiol 31(3);833-44. PMID: 10048027

Rhodius05: Rhodius VA, Suh WC, Nonaka G, West J, Gross CA (2005). "Conserved and variable functions of the sigmaE stress response in related genomes." PLoS Biol 4(1);e2. PMID: 16336047

Schakermann13: Schakermann M, Langklotz S, Narberhaus F (2013). "FtsH-mediated coordination of lipopolysaccharide biosynthesis in Escherichia coli correlates with the growth rate and the alarmone (p)ppGpp." J Bacteriol 195(9);1912-9. PMID: 23417489

Tomasiewicz87: Tomasiewicz HG, McHenry CS (1987). "Sequence analysis of the Escherichia coli dnaE gene." J Bacteriol 1987;169(12);5735-44. PMID: 3316192

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

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

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

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

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

Zeng13: Zeng D, Zhao J, Chung HS, Guan Z, Raetz CR, Zhou P (2013). "Mutants resistant to LpxC inhibitors by rebalancing cellular homeostasis." J Biol Chem 288(8);5475-86. PMID: 23316051

Other References Related to Gene Regulation

Hommais04: Hommais F, Krin E, Coppee JY, Lacroix C, Yeramian E, Danchin A, Bertin P (2004). "GadE (YhiE): a novel activator involved in the response to acid environment in Escherichia coli." Microbiology 150(Pt 1);61-72. PMID: 14702398


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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 Mon Dec 22, 2014, biocyc13.