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Escherichia coli K-12 substr. MG1655 Enzyme: fatty acid oxidation complex, α component



Gene: fadB Accession Numbers: EG10279 (EcoCyc), b3846, ECK3838

Synonyms: oldB

Regulation Summary Diagram: ?

Component of: aerobic fatty acid oxidation complex

Subunit composition of fatty acid oxidation complex, α component = [FadB]2
         dodecenoyl-CoA δ-isomerase, enoyl-CoA hydratase, 3-hydroxybutyryl-CoA epimerase, 3-hydroxyacyl-CoA dehydrogenase = FadB

Summary:
The alpha subunit has four enzymatic activities associated with it. It is part of a multienzyme complex. Two of the activities, enoyl-CoA hydratase (EC 4.2.1.17) and 3-OHacyl-CoA epimerase (EC 5.1.2.3) are carried out by the same N terminal active site. [Yang93]

Gene Citations: [Yang91, Yang91a]

Locations: cytosol

Map Position: [4,026,805 <- 4,028,994] (86.79 centisomes)
Length: 2190 bp / 729 aa

Molecular Weight of Polypeptide: 79.594 kD (from nucleotide sequence)

pI: 6.16

Unification Links: ASAP:ABE-0012564 , CGSC:793 , DIP:DIP-9560N , EchoBASE:EB0275 , EcoGene:EG10279 , EcoliWiki:b3846 , ModBase:P21177 , OU-Microarray:b3846 , PortEco:fadB , Pride:P21177 , Protein Model Portal:P21177 , RefSeq:NP_418288 , RegulonDB:EG10279 , SMR:P21177 , String:511145.b3846 , Swiss-Model:P21177 , UniProt:P21177

Relationship Links: InterPro:IN-FAMILY:IPR001753 , InterPro:IN-FAMILY:IPR006108 , InterPro:IN-FAMILY:IPR006176 , InterPro:IN-FAMILY:IPR006180 , InterPro:IN-FAMILY:IPR008927 , InterPro:IN-FAMILY:IPR012799 , InterPro:IN-FAMILY:IPR013328 , InterPro:IN-FAMILY:IPR016040 , InterPro:IN-FAMILY:IPR018376 , Pfam:IN-FAMILY:PF00378 , Pfam:IN-FAMILY:PF00725 , Pfam:IN-FAMILY:PF02737 , Prosite:IN-FAMILY:PS00067 , Prosite:IN-FAMILY:PS00166

In Paralogous Gene Group: 12 (7 members) , 285 (5 members)

Gene-Reaction Schematic: ?

Instance reaction of [a cis-3-enoyl-CoA ↔ a trans-2-enoyl-CoA] (5.3.3.8):
i1: 3-cis-dodecenoyl-CoA = 2-trans-dodecenoyl-CoA (5.3.3.8)

Instance reaction of [a (3S)-3-hydroxyacyl-CoA + NAD+ ↔ a 3-oxoacyl-CoA + NADH + H+] (1.1.1.35):
i2: 3-hydroxy-5-cis-tetradecenoyl-CoA + NAD+ = 3-keto-5-cis-tetradecenoyl-CoA + NADH + H+ (1.1.1.211)

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0006635 - fatty acid beta-oxidation Inferred from experiment Inferred by computational analysis [UniProtGOA12, Pramanik79]
GO:0006629 - lipid metabolic process Inferred by computational analysis [UniProtGOA11a]
GO:0006631 - fatty acid metabolic process Inferred by computational analysis [UniProtGOA11a, GOA06, GOA01a]
GO:0008152 - metabolic process Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0009062 - fatty acid catabolic process Inferred by computational analysis [GOA01a]
GO:0016042 - lipid catabolic process Inferred by computational analysis [UniProtGOA11a, GOA06]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11a, GOA01a]
Molecular Function: GO:0003857 - 3-hydroxyacyl-CoA dehydrogenase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01, GOA01a, He96]
GO:0004165 - dodecenoyl-CoA delta-isomerase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01, GOA01a, Pramanik79]
GO:0004300 - enoyl-CoA hydratase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01, GOA01a, Yang93]
GO:0008692 - 3-hydroxybutyryl-CoA epimerase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01, GOA01a, Yang93]
GO:0003824 - catalytic activity Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0016616 - oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor Inferred by computational analysis [GOA01a]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016853 - isomerase activity Inferred by computational analysis [UniProtGOA11a]
GO:0050662 - coenzyme binding Inferred by computational analysis [GOA01a]
Cellular Component: GO:0005829 - cytosol
GO:0036125 - fatty acid beta-oxidation multienzyme complex Inferred by computational analysis [GOA01a]

MultiFun Terms: metabolism carbon utilization fatty acids

Essentiality data for fadB knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
Yes [Feist07, Comment 4]

Enzymatic reaction of: 3-hydroxyacyl-CoA dehydrogenase (fatty acid oxidation complex, α component)

EC Number: 1.1.1.211

3-hydroxy-5-cis-tetradecenoyl-CoA + NAD+ <=> 3-keto-5-cis-tetradecenoyl-CoA + 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.

Summary:
Experimental work reported by [Ren04a] was conducted using E. coli strain B.


Enzymatic reaction of: 3-hydroxybutyryl-CoA epimerase (fatty acid oxidation complex, α component)

Synonyms: 3-hydroxyacyl-CoA epimerase, 3-hydroxybutanoyl-CoA 3-epimerase

EC Number: 5.1.2.3

a (3R)-3-hydroxyacyl-CoA <=> a (3S)-3-hydroxyacyl-CoA

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

This reaction is reversible.

Alternative Substrates [Comment 5]:

In Pathways: fatty acid β-oxidation I

Summary:
This enzyme is part of a multienzyme complex that has broad substrate specificity. It is also part of a multifunctional polypeptide coded for by the fadB gene. This enzyme is required to feed some unsaturated fatty acids into the β-oxidation pathway. [Pramanik79] The active site for this reaction is also involved in the hydratase reaction (EC 4.2.1.17).

Regulators of Unknown Type: iodoacetamide [Yang83] , tris-hydrochloride [Pramanik79]


Enzymatic reaction of: 3-hydroxyacyl-CoA dehydrogenase (fatty acid oxidation complex, α component)

Synonyms: β-hydroxyacyl dehydrogenase, β-keto-reductase, (S)-3-hydroxyacyl-CoA:NAD+ oxidoreductase

EC Number: 1.1.1.35

a (3S)-3-hydroxyacyl-CoA + NAD+ <=> a 3-oxoacyl-CoA + NADH + H+

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

This reaction is reversible.

Alternative Substrates for a (3S)-3-hydroxyacyl-CoA: a S-3-hydroxyacyl-N-acylthioethanolamine , a S-3-hydroxyacylhydrolipoate

In Pathways: fatty acid β-oxidation I

Summary:
This enzyme is part of a multienzyme complex that has broad substrate specificity. It is also part of a multifunctional polypeptide coded for by the fadB gene. This enzyme takes part in the oxidation of saturated fatty acids. It exhibits the highest activity with medium-chain substrates. [Binstock81] It also oxidizes S-3-hydroxyacyl-N-acylthioethanolamine and S-3-hydroxyacylhydrolipoate.

Regulators of Unknown Type: iodoacetamide [Yang83] , tris-hydrochloride [Pramanik79]


Enzymatic reaction of: enoyl-CoA hydratase (fatty acid oxidation complex, α component)

Synonyms: enoyl hydrase, unsaturated acyl-CoA hydratase, (3S)-3-hydroxyacyl-CoA hydro-lyase

EC Number: 4.2.1.17

a (3S)-3-hydroxyacyl-CoA <=> a trans-2-enoyl-CoA + 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 physiologically favored in the opposite direction.

EC Number: 4.2.1.17

2-trans,5-cis-tetradecadienoyl-CoA + H2O <=> 3-hydroxy-5-cis-tetradecenoyl-CoA

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

Alternative Substrates [Comment 5]:

In Pathways: oleate β-oxidation , fatty acid β-oxidation I

Summary:
This enzyme, a crotonase, is part of a multienzyme complex that has broad substrate specificity. It is also part of a multifunctional polypeptide coded for by the fadB gene. This enzyme takes part in the oxidation of saturated fatty acids. The enzyme is active with substrates of varying chain lengths. [Binstock81] The active site also catalyzes epimerization of unsaturated fatty acids (EC 5.1.2.3). [Yang93]

Regulators of Unknown Type: iodoacetamide [Yang83] , tris-hydrochloride [Pramanik79]


Enzymatic reaction of: Δ3-cis-Δ2-trans-enoyl-CoA isomerase (fatty acid oxidation complex, α component)

Synonyms: dodecenoyl-CoA δ-isomerase, enoyl-CoA δ-isomerase, acetylene-allene isomerase, dodecenoyl-CoA δ(3)-cis-δ(2)-trans-isomerase

a cis-3-enoyl-CoA <=> a trans-2-enoyl-CoA

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

This reaction is reversible.

2-trans,5-cis-tetradecadienoyl-CoA <=> 3-trans,5-cis-tetradecadienoyl-CoA

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

This reaction is reversible.

In Pathways: oleate β-oxidation , fatty acid β-oxidation I

Summary:
This enzyme is part of a multienzyme complex that has broad substrate specificity. It is also part of a multifunctional polypeptide coded for by the fadB gene. This enzyme is required when carbons 3,4 unsaturated fatty acids are degraded. [Pramanik79] It also catalyses the interconversion of 3-acetylenic fatty acyl thioesters and (+)-2,3-dienoyl fatty acyl thioesters, with fatty acid chain lengths C(6) to C(12).

Regulators of Unknown Type: N-ethylmaleimide [Pawar81] , iodoacetamide [Yang83] , tris-hydrochloride [Pramanik79]


Subunit of: aerobic fatty acid oxidation complex

Subunit composition of aerobic fatty acid oxidation complex = [(FadB)2][(FadA)2]
         fatty acid oxidation complex, α component = (FadB)2 (summary available)
                 dodecenoyl-CoA δ-isomerase, enoyl-CoA hydratase, 3-hydroxybutyryl-CoA epimerase, 3-hydroxyacyl-CoA dehydrogenase = FadB
         fatty acid oxidation complex, β component = (FadA)2
                 3-ketoacyl-CoA thiolase = FadA


Sequence Features

Feature Class Location Citations Comment
Protein-Segment 1 -> 189
[UniProt10a]
UniProt: Enoyl-CoA hydratase/isomerase; Sequence Annotation Type: region of interest;
Mutagenesis-Variant 116
[Yang93, UniProt14]
Alternate sequence: G → F; UniProt: Absence of both enoyl-CoA hydratase and 3-hydroxyacyl-CoA epimerase activities. Delta(3)-cis-Delta(2)-trans- enoyl-CoA isomerase is only slightly affected.
Amino-Acid-Site 119
[UniProt10a]
UniProt: Important for catalytic activity; Sequence Annotation Type: site; Non-Experimental Qualifier: by similarity;
Amino-Acid-Site 139
[UniProt10a]
UniProt: Important for catalytic activity; Sequence Annotation Type: site; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 296
[UniProt10a]
UniProt: Substrate; Non-Experimental Qualifier: by similarity;
Protein-Segment 311 -> 729
[UniProt10a]
UniProt: 3-hydroxyacyl-CoA dehydrogenase; Sequence Annotation Type: region of interest;
Mutagenesis-Variant 322
[He96, UniProt11]
Alternate sequence: G → A; UniProt: 10-fold increase in KM for NADH.
Amino-Acid-Sites-That-Bind 324
[UniProt10a]
UniProt: NAD; via amide nitrogen; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 343
[UniProt10a]
UniProt: NAD; Non-Experimental Qualifier: by similarity;
Nucleotide-Phosphate-Binding-Region 400 -> 402
[UniProt10a]
UniProt: NAD; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 407
[UniProt10a]
UniProt: NAD; Non-Experimental Qualifier: by similarity;
Nucleotide-Phosphate-Binding-Region 427 -> 429
[UniProt10a]
UniProt: NAD; Non-Experimental Qualifier: by similarity;
Mutagenesis-Variant 450
[He96, UniProt11]
Alternate sequence: H → Q; UniProt: Almost complete loss of 3- hydroxyacyl-CoA dehydrogenase activity.
Alternate sequence: H → A; UniProt: Almost complete loss of 3- hydroxyacyl-CoA dehydrogenase activity.
Active-Site 450
[Yang93, He96, UniProt11]
UniProt: For 3-hydroxyacyl-CoA dehydrogenase activity.
Amino-Acid-Sites-That-Bind 453
[UniProt10a]
UniProt: NAD; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 500
[UniProt10a]
UniProt: Substrate; Non-Experimental Qualifier: by similarity;
Sequence-Conflict 518
[DiRusso90, UniProt10]
Alternate sequence: A → R; UniProt: (in Ref. 1; AAA23750);
Amino-Acid-Sites-That-Bind 660
[UniProt10a]
UniProt: Substrate; Non-Experimental Qualifier: by similarity;
Sequence-Conflict 664
[Nakahigashi90, UniProt10]
Alternate sequence: F → L; UniProt: (in Ref. 3; CAB40809);
Sequence-Conflict 666
[Nakahigashi90, UniProt10]
Alternate sequence: P → A; UniProt: (in Ref. 3; CAB40809);


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
10/20/97 Gene b3846 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10279; 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

Binstock81: Binstock JF, Schulz H (1981). "Fatty acid oxidation complex from Escherichia coli." Methods Enzymol 1981;71 Pt C;403-11. PMID: 7024730

DiRusso90: DiRusso CC (1990). "Primary sequence of the Escherichia coli fadBA operon, encoding the fatty acid-oxidizing multienzyme complex, indicates a high degree of homology to eucaryotic enzymes." J Bacteriol 172(11);6459-68. PMID: 1699931

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

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

He96: He XY, Yang SY (1996). "Histidine-450 is the catalytic residue of L-3-hydroxyacyl coenzyme A dehydrogenase associated with the large alpha-subunit of the multienzyme complex of fatty acid oxidation from Escherichia coli." Biochemistry 1996;35(29);9625-30. PMID: 8755745

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Nakahigashi90: Nakahigashi K, Inokuchi H (1990). "Nucleotide sequence of the fadA and fadB genes from Escherichia coli." Nucleic Acids Res 18(16);4937. PMID: 2204034

Pawar81: Pawar S, Schulz H (1981). "The structure of the multienzyme complex of fatty acid oxidation from Escherichia coli." J Biol Chem 1981;256(8);3894-9. PMID: 7012144

Pramanik79: Pramanik A, Pawar S, Antonian E, Schulz H (1979). "Five different enzymatic activities are associated with the multienzyme complex of fatty acid oxidation from Escherichia coli." J Bacteriol 1979;137(1);469-73. PMID: 368024

Ren04a: Ren Y, Aguirre J, Ntamack AG, Chu C, Schulz H (2004). "An alternative pathway of oleate beta-oxidation in Escherichia coli involving the hydrolysis of a dead end intermediate by a thioesterase." J Biol Chem 279(12);11042-50. PMID: 14707139

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

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.

UniProt14: UniProt Consortium (2014). "UniProt version 2014-01 released on 2014-01-01 00:00:00." Database.

UniProtGOA11a: 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."

Yang83: Yang SY, Schulz H (1983). "The large subunit of the fatty acid oxidation complex from Escherichia coli is a multifunctional polypeptide. Evidence for the existence of a fatty acid oxidation operon (fad AB) in Escherichia coli." J Biol Chem 1983;258(16);9780-5. PMID: 6350283

Yang91: Yang XY, Schulz H, Elzinga M, Yang SY (1991). "Nucleotide sequence of the promoter and fadB gene of the fadBA operon and primary structure of the multifunctional fatty acid oxidation protein from Escherichia coli." Biochemistry 1991;30(27);6788-95. PMID: 1712230

Yang91a: Yang SY (1991). "Location of the fadBA operon on the physical map of Escherichia coli." J Bacteriol 1991;173(23);7405-6. PMID: 1938932

Yang93: Yang SY, Elzinga M (1993). "Association of both enoyl coenzyme A hydratase and 3-hydroxyacyl coenzyme A epimerase with an active site in the amino-terminal domain of the multifunctional fatty acid oxidation protein from Escherichia coli." J Biol Chem 1993;268(9);6588-92. PMID: 8454629

Yang95: Yang SY, He XY, Schulz H (1995). "Glutamate 139 of the large alpha-subunit is the catalytic base in the dehydration of both D- and L-3-hydroxyacyl-coenzyme A but not in the isomerization of delta 3, delta 2-enoyl-coenzyme A catalyzed by the multienzyme complex of fatty acid oxidation from Escherichia coli." Biochemistry 1995;34(19);6441-7. PMID: 7756275

Other References Related to Gene Regulation

Bradley07: Bradley MD, Beach MB, de Koning AP, Pratt TS, Osuna R (2007). "Effects of Fis on Escherichia coli gene expression during different growth stages." Microbiology 153(Pt 9);2922-40. PMID: 17768236

Cho06: Cho BK, Knight EM, Palsson BO (2006). "Transcriptional regulation of the fad regulon genes of Escherichia coli by ArcA." Microbiology 152(Pt 8);2207-19. PMID: 16849788

DiRusso92: DiRusso CC, Heimert TL, Metzger AK (1992). "Characterization of FadR, a global transcriptional regulator of fatty acid metabolism in Escherichia coli. Interaction with the fadB promoter is prevented by long chain fatty acyl coenzyme A." J Biol Chem 1992;267(12);8685-91. PMID: 1569108

DiRusso99: DiRusso CC, Black PN, Weimar JD (1999). "Molecular inroads into the regulation and metabolism of fatty acids, lessons from bacteria." Prog Lipid Res 38(2);129-97. PMID: 10396600

Gui96: Gui L, Sunnarborg A, LaPorte DC (1996). "Regulated expression of a repressor protein: FadR activates iclR." J Bacteriol 1996;178(15);4704-9. PMID: 8755903

Liu04: Liu X, De Wulf P (2004). "Probing the ArcA-P modulon of Escherichia coli by whole genome transcriptional analysis and sequence recognition profiling." J Biol Chem 279(13);12588-97. PMID: 14711822

Spiro91: Spiro S, Guest JR (1991). "Adaptive responses to oxygen limitation in Escherichia coli." Trends Biochem Sci 1991;16(8);310-4. PMID: 1957353


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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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