Escherichia coli K-12 substr. MG1655 Enzyme: KASII

Gene: fabF Accession Numbers: EG12606 (EcoCyc), b1095, ECK1081

Synonyms: vtr, cvc, fabJ, vtrB, 3-oxoacyl-ACP synthase II, KASII, acyl-[acyl carrier protein]:malonyl-[acyl carrier protein] C-acyltransferase (decarboxylating), β ketoacyl-acyl carrier protein synthase I, β-ketoacyl-ACP synthase II

Regulation Summary Diagram: ?

Regulation summary diagram for fabF

Subunit composition of KASII = [FabF]2

There are three β-ketoacyl-ACP synthases (KAS) in E. coli: KASI, KASII and KASIII, encoded by fabB, fabF and fabH, respectively. All three are genetically and biochemically distinct. Each of the three enzymes is capable of initiating fatty acid biosynthesis.

KASII is the only enzyme that can catalyze the conversion of palmitoleate to cis-vaccenate, and is believed to play a major role in the thermal regulation of fatty acid composition of the membrane phospholipids of E. coli [Garwin80a].

The only unsaturated fatty acids found in E. coli, palmitoleate and cis-vaccenate, comprise about one-half the fatty acid content of the organism. The proportion of unsaturated fatty acids is known to increase in E. coli with lower growth temperature, a phenomenon found in most organisms that provides a mechanism for adjusting the lipid phase transition of the membrane phospholipids to differing temperatures.

It has been shown that KASII is more active at low temperatures (relative to the overall rate of fatty acid synthesis) than at high temperatures [Garwin80]. This relative increase results in the production of cis-vaccenate rather than palmitoleate. Furthermore, because the former (but not the later) can be incorporated into both positions of sn-glycerol 3-phosphate, the synthesis of diunsaturated phospholipids occurs and the thermotrophic phase transition of the membrane phospholipids is lowered [Garwin80a].

FabF is composed of two identical subunits. The apparent molecular masses of the native protein and the subunit were determined by sedimentation equilibrium and SDS-PAGE, respectively [Garwin80].

The crystal structure of the enzyme [Huang98c, Wang06] and the enzyme in complex with the inhibitor cerulenin [Moche99] have been determined. Crystal structures of a mutant enzyme [Wang06], a mutant enzyme with covalently linked dodecanoate, a mutant enzyme in complex with the inhibitor platensimycin [Wang06], and mutant enzymes in complex with platensimycin analogs have also been determined [Wang06, Shen09b, Singh09a].

In metabolic engineering studies aimed at biofuel production, overexpression of the fatty acid elongation cycle enzymes, including FabF, has been used to increase long-chain fatty acid synthesis in E. coli [Lee13, Yu11a]. Inclusion of the regulatory transcription factor FadR enhanced production and produced largest transcriptional changes in fabB, fabF, and accA [Zhang12a].

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

Gene Citations: [Magnuson95, Edwards97, Zhang96e]

Locations: cytosol

Map Position: [1,151,162 -> 1,152,403] (24.81 centisomes, 89°)
Length: 1242 bp / 413 aa

Molecular Weight of Polypeptide: 43.046 kD (from nucleotide sequence), 44.0 kD (experimental) [Garwin80 ]

Molecular Weight of Multimer: 85.0 kD (experimental) [Garwin80]

Isozyme Sequence Similarity:
FabB: NO

Unification Links: ASAP:ABE-0003705 , CGSC:795 , DIP:DIP-29377N , EchoBASE:EB2490 , EcoGene:EG12606 , EcoliWiki:b1095 , Mint:MINT-1231688 , OU-Microarray:b1095 , PortEco:fabF , PR:PRO_000022562 , Pride:P0AAI5 , Protein Model Portal:P0AAI5 , RefSeq:NP_415613 , RegulonDB:EG12606 , SMR:P0AAI5 , String:511145.b1095 , UniProt:P0AAI5

Relationship Links: InterPro:IN-FAMILY:IPR014030 , InterPro:IN-FAMILY:IPR014031 , InterPro:IN-FAMILY:IPR016038 , InterPro:IN-FAMILY:IPR016039 , InterPro:IN-FAMILY:IPR017568 , InterPro:IN-FAMILY:IPR018201 , PDB:Structure:1B3N , PDB:Structure:1KAS , PDB:Structure:2GFV , PDB:Structure:2GFW , PDB:Structure:2GFX , PDB:Structure:2GFY , PDB:Structure:3G0Y , PDB:Structure:3G11 , PDB:Structure:3HNZ , PDB:Structure:3HO2 , PDB:Structure:3HO9 , PDB:Structure:3I8P , Pfam:IN-FAMILY:PF00109 , Pfam:IN-FAMILY:PF02801 , Prosite:IN-FAMILY:PS00606

In Paralogous Gene Group: 408 (2 members)

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for fabF

GO Terms:

Biological Process: 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:0008152 - metabolic process Inferred by computational analysis [GOA01]
Molecular Function: GO:0004315 - 3-oxoacyl-[acyl-carrier-protein] synthase activity Inferred from experiment [DAgnolo75]
GO:0005515 - protein binding Inferred from experiment [Butland05]
GO:0033817 - beta-ketoacyl-acyl-carrier-protein synthase II activity Inferred from experiment Inferred by computational analysis [GOA01a, Jackowski87a, Garwin80]
GO:0042803 - protein homodimerization activity Inferred from experiment [Garwin80]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11]
GO:0016746 - transferase activity, transferring acyl groups Inferred by computational analysis [UniProtGOA11]
GO:0016747 - transferase activity, transferring acyl groups other than amino-acyl groups Inferred by computational analysis [GOA01]
Cellular Component: GO:0005829 - cytosol Inferred from experiment [Lasserre06]

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

Essentiality data for fabF 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]

Last-Curated ? 15-Apr-2013 by Fulcher C , SRI International

Enzymatic reaction of: 3-oxo-cis-vaccenoyl-[acp] synthase (KASII)

EC Number:

a palmitoleoyl-[acp] + a malonyl-[acp] + H+ <=> a 3-oxo-cis-vacc-11-enoyl-[acp] + CO2 + a holo-[acyl-carrier protein]

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

Enzymatic reaction of: acetoacetyl-[acp] synthase (KASII)

EC Number:

a malonyl-[acp] + an acetyl-[acp] + H+ <=> a holo-[acyl-carrier protein] + an acetoacetyl-[acp] + CO2

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 fatty acid biosynthesis initiation (E. coli) , fatty acid biosynthesis initiation II , fatty acid biosynthesis initiation III

Inhibitors (Unknown Mechanism): thiolactomycin [Jackowski89] , cerulenin [Jackowski87]

Enzymatic reaction of: β-ketoacyl-ACP synthase (KASII)

Synonyms: 3-oxoacyl-ACP synthase, decarboxylating acyltransferase

EC Number:

a malonyl-[acp] + a 2,3,4-saturated fatty acyl-[acp] + H+ <=> a holo-[acyl-carrier protein] + a 3-oxoacyl-[acp] + CO2

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) , fatty acid elongation -- saturated

The enzyme can also utilize substrates that are CoA thioesters [Machutta10, Wang06, Alberts72, Borgaro11]. A 14 residue malonyl-phosphopantetheine peptide was shown to efficiently function as an acceptor substrate in the FabF reaction [Borgaro11]. Kinetic parameters for substrates malonyl-[acp] and lauroyl-[acp] (dodecanoyl-[acp]) have been determined [Borgaro11].

Inhibitors (Unknown Mechanism): platensimycin [Wang06] , thiolactomycin [Jackowski89] , cerulenin [Jackowski87, Comment 5]

Sequence Features

Protein sequence of FabF with features indicated

Feature Class Location Citations Comment
Cleavage-of-Initial-Methionine 1
[SiggaardAnderse94, UniProt11]
UniProt: Removed.
Chain 2 -> 413
UniProt: 3-oxoacyl-[acyl-carrier-protein] synthase 2;
Active-Site 164
[Moche99, UniProt15]

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b1095 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG12606; confirmed by SwissProt match.


Alberts72: Alberts AW, Bell RM, Vagelos PR (1972). "Acyl carrier protein. XV. Studies of -ketoacyl-acyl carrier protein synthetase." J Biol Chem 247(10);3190-8. PMID: 5027749

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

Borgaro11: Borgaro JG, Chang A, Machutta CA, Zhang X, Tonge PJ (2011). "Substrate recognition by β-ketoacyl-ACP synthases." Biochemistry 50(49);10678-86. PMID: 22017312

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

DAgnolo75: D'Agnolo G, Rosenfeld IS, Vagelos PR (1975). "Multiple forms of beta-ketoacyl-acyl carrier protein synthetase in Escherichia coli." J Biol Chem 250(14);5289-94. PMID: 237914

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

Edwards97: Edwards P, Nelsen JS, Metz JG, Dehesh K (1997). "Cloning of the fabF gene in an expression vector and in vitro characterization of recombinant fabF and fabB encoded enzymes from Escherichia coli." FEBS Lett 402(1);62-6. PMID: 9013860

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

Garwin80: Garwin JL, Klages AL, Cronan JE (1980). "Structural, enzymatic, and genetic studies of beta-ketoacyl-acyl carrier protein synthases I and II of Escherichia coli." J Biol Chem 1980;255(24);11949-56. PMID: 7002930

Garwin80a: Garwin JL, Klages AL, Cronan JE (1980). "Beta-ketoacyl-acyl carrier protein synthase II of Escherichia coli. Evidence for function in the thermal regulation of fatty acid synthesis." J Biol Chem 1980;255(8);3263-5. PMID: 6988423

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, 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.

Huang98c: Huang W, Jia J, Edwards P, Dehesh K, Schneider G, Lindqvist Y (1998). "Crystal structure of beta-ketoacyl-acyl carrier protein synthase II from E.coli reveals the molecular architecture of condensing enzymes." EMBO J 17(5);1183-91. PMID: 9482715

Jackowski87: Jackowski S, Rock CO (1987). "Acetoacetyl-acyl carrier protein synthase, a potential regulator of fatty acid biosynthesis in bacteria." J Biol Chem 1987;262(16);7927-31. PMID: 3294837

Jackowski87a: Jackowski S, Rock CO (1987). "Altered molecular form of acyl carrier protein associated with beta-ketoacyl-acyl carrier protein synthase II (fabF) mutants." J Bacteriol 169(4);1469-73. PMID: 3549687

Jackowski89: Jackowski S, Murphy CM, Cronan JE, Rock CO (1989). "Acetoacetyl-acyl carrier protein synthase. A target for the antibiotic thiolactomycin." J Biol Chem 1989;264(13);7624-9. PMID: 2651445

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

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

Lee13: 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

Machutta10: Machutta CA, Bommineni GR, Luckner SR, Kapilashrami K, Ruzsicska B, Simmerling C, Kisker C, Tonge PJ (2010). "Slow onset inhibition of bacterial beta-ketoacyl-acyl carrier protein synthases by thiolactomycin." J Biol Chem 285(9);6161-9. PMID: 20018879

Magnuson95: Magnuson K, Carey MR, Cronan JE (1995). "The putative fabJ gene of Escherichia coli fatty acid synthesis is the fabF gene." J Bacteriol 177(12);3593-5. PMID: 7768872

Moche99: Moche M, Schneider G, Edwards P, Dehesh K, Lindqvist Y (1999). "Structure of the complex between the antibiotic cerulenin and its target, beta-ketoacyl-acyl carrier protein synthase." J Biol Chem 274(10);6031-4. PMID: 10037680

Shen09b: Shen HC, Ding FX, Singh SB, Parthasarathy G, Soisson SM, Ha SN, Chen X, Kodali S, Wang J, Dorso K, Tata JR, Hammond ML, Maccoss M, Colletti SL (2009). "Synthesis and biological evaluation of platensimycin analogs." Bioorg Med Chem Lett 19(6);1623-7. PMID: 19233644

SiggaardAnderse94: Siggaard-Andersen M, Wissenbach M, Chuck JA, Svendsen I, Olsen JG, von Wettstein-Knowles P (1994). "The fabJ-encoded beta-ketoacyl-[acyl carrier protein] synthase IV from Escherichia coli is sensitive to cerulenin and specific for short-chain substrates." Proc Natl Acad Sci U S A 91(23);11027-31. PMID: 7972002

Singh09a: Singh SB, Ondeyka JG, Herath KB, Zhang C, Jayasuriya H, Zink DL, Parthasarathy G, Becker JW, Wang J, Soisson SM (2009). "Isolation, enzyme-bound structure and antibacterial activity of platencin A1 from Streptomyces platensis." Bioorg Med Chem Lett 19(16);4756-9. PMID: 19581087

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

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

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 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."

Wang06: Wang J, Soisson SM, Young K, Shoop W, Kodali S, Galgoci A, Painter R, Parthasarathy G, Tang YS, Cummings R, Ha S, Dorso K, Motyl M, Jayasuriya H, Ondeyka J, Herath K, Zhang C, Hernandez L, Allocco J, Basilio A, Tormo JR, Genilloud O, Vicente F, Pelaez F, Colwell L, Lee SH, Michael B, Felcetto T, Gill C, Silver LL, Hermes JD, Bartizal K, Barrett J, Schmatz D, Becker JW, Cully D, Singh SB (2006). "Platensimycin is a selective FabF inhibitor with potent antibiotic properties." Nature 441(7091);358-61. PMID: 16710421

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

Yu11a: 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

Zhang12a: Zhang F, Ouellet M, Batth TS, Adams PD, Petzold CJ, Mukhopadhyay A, Keasling JD (2012). "Enhancing fatty acid production by the expression of the regulatory transcription factor FadR." Metab Eng 14(6);653-60. PMID: 23026122

Zhang96e: Zhang Y, Cronan JE (1996). "Polar allele duplication for transcriptional analysis of consecutive essential genes: application to a cluster of Escherichia coli fatty acid biosynthetic genes." J Bacteriol 1996;178(12);3614-20. PMID: 8655562

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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 19.0 on Thu Oct 8, 2015, biocyc12.