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MetaCyc Engineered Pathway: methyl ketone biosynthesis
Inferred from experiment

Enzyme View:

Pathway diagram: methyl ketone biosynthesis

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Generation of Precursor Metabolites and Energy

Note: This is an engineered pathway. It does not occur naturally in any known organism, and has been constructed in a living cell by metabolic engineering.

The enzymes catalyzing the steps of this pathway have been assembled from the following organisms : Escherichia coli K-12 substr. MG1655, Lycopersicon hirsutum glabratum, Micrococcus luteus, Solanum lycopersicum


2-tridecanone is an aliphatic methyl ketone that is naturally occurring in plants, where it can play a role as both a pheromone and insecticide [Antonious03]. The methyl ketone biosynthetic pathway was characterized in tomato plants, specifically Solanum habrochaites, from which two key genes ( MKS1 and MKS2) were identified that were required for methyl ketone synthesis from fatty acid intermediates [Yu10]. MKS1 is purported to hydrolyze a β-ketoacyl ACP to generate a β-keto acid, and MKS2 may decarboxylate the β-keto acid to a methyl ketone (see 2-methylketone biosynthesis).

Being a reduced aliphatic compound, methyl ketones may have relevance as a biofuel, and recently Escherichia coli has been metabolically engineered to overproduce methyl ketones with application to biofuel production [Goh12].

About this Pathway

To successfully create this synthetic pathway akin to a truncated form of the fatty acid β-oxidation I pathway in Escherichia coli, two key genes of this pathway, fadE and fadA were deleted. The reaction catalyzed by fadE was reconstituted by cloning the gene for acyl-CoA oxidase from Micrococcus luteus. This was done to replace membrane associated fadE with a highly soluble enzyme and Micrococcus luteus acyl-Co oxidase has homology to a high activity acyl coA oxidase from Arthrobacter ureafaciens. The fadA gene was knocked out to push the pathway towards β-keto acid production. The genes fadB and fadM were overexpressed to optimize methyl ketone biosynthesis.

Created 02-Mar-2012 by Weerasinghe D, SRI International


Antonious03: Antonious GF, Dahlman DL, Hawkins LM (2003). "Insecticidal and acaricidal performance of methyl ketones in wild tomato leaves." Bull Environ Contam Toxicol 71(2);400-7. PMID: 14560395

Goh12: Goh EB, Baidoo EE, Keasling JD, Beller HR (2012). "Engineering of bacterial methyl ketone synthesis for biofuels." Appl Environ Microbiol 78(1);70-80. PMID: 22038610

Yu10: Yu G, Nguyen TT, Guo Y, Schauvinhold I, Auldridge ME, Bhuiyan N, Ben-Israel I, Iijima Y, Fridman E, Noel JP, Pichersky E (2010). "Enzymatic functions of wild tomato methylketone synthases 1 and 2." Plant Physiol 154(1);67-77. PMID: 20605911

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Adham05: Adham AR, Zolman BK, Millius A, Bartel B (2005). "Mutations in Arabidopsis acyl-CoA oxidase genes reveal distinct and overlapping roles in beta-oxidation." Plant J 41(6);859-74. PMID: 15743450

Bakke07: Bakke M, Setoyama C, Miura R, Kajiyama N (2007). "N-ethylmaleimide-resistant acyl-coenzyme A oxidase from Arthrobacter ureafaciens NBRC 12140: molecular cloning, gene expression and characterization of the recombinant enzyme." Biochim Biophys Acta 1774(1);65-71. PMID: 17141592

Begrends88: Begrends, Wilke, Engeland, Kurt, Kindl, Helmut (1988). "Characterization of two forms of the multifunctional protein acting in fatty acid beta-oxidation." Arch Biochem Biophys, 263(1): 161-1691.

Beloin04: Beloin C, Valle J, Latour-Lambert P, Faure P, Kzreminski M, Balestrino D, Haagensen JA, Molin S, Prensier G, Arbeille B, Ghigo JM (2004). "Global impact of mature biofilm lifestyle on Escherichia coli K-12 gene expression." Mol Microbiol 51(3);659-74. PMID: 14731270

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

Campbell03: Campbell JW, Morgan-Kiss RM, E Cronan J (2003). "A new Escherichia coli metabolic competency: growth on fatty acids by a novel anaerobic beta-oxidation pathway." Mol Microbiol 47(3);793-805. PMID: 12535077

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Eastmond00: Eastmond PJ, Hooks MA, Williams D, Lange P, Bechtold N, Sarrobert C, Nussaume L, Graham IA (2000). "Promoter trapping of a novel medium-chain acyl-CoA oxidase, which is induced transcriptionally during Arabidopsis seed germination." J Biol Chem 275(44);34375-81. PMID: 10918060

Ferdinandusse04: Ferdinandusse S, Denis S, Van Roermund CW, Wanders RJ, Dacremont G (2004). "Identification of the peroxisomal beta-oxidation enzymes involved in the degradation of long-chain dicarboxylic acids." J Lipid Res 45(6);1104-11. PMID: 15060085

Fridman05: Fridman E, Wang J, Iijima Y, Froehlich JE, Gang DR, Ohlrogge J, Pichersky E (2005). "Metabolic, genomic, and biochemical analyses of glandular trichomes from the wild tomato species Lycopersicon hirsutum identify a key enzyme in the biosynthesis of methylketones." Plant Cell 17(4);1252-67. PMID: 15772286

Froman00: Froman BE, Edwards PC, Bursch AG, Dehesh K (2000). "ACX3, a novel medium-chain acyl-coenzyme A oxidase from Arabidopsis." Plant Physiol 123(2);733-42. PMID: 10859203

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."

GuhnemannSchafe95: Guhnemann-Schafer K, Kindl H (1995). "Fatty acid beta-oxidation in glyoxysomes. Characterization of a new tetrafunctional protein (MFP III)." Biochim Biophys Acta 1256(2);181-6. PMID: 7766696

GuhnemannShafer94: Guhnemann-Shafer, Kerstin, Engeland, Kurt, Linder, Dietmar, Kindl, Helmut (1994). "Evidence for domain structures of the trifunctional protein and tetrafunctional protein acting in glyoxysomal fatty acid beta-oxidation." Eur J Biochem, 226: 909-915.

Hayashi99: Hayashi H, De Bellis L, Ciurli A, Kondo M, Hayashi M, Nishimura M (1999). "A novel acyl-CoA oxidase that can oxidize short-chain acyl-CoA in plant peroxisomes." J Biol Chem 274(18);12715-21. PMID: 10212254

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

Hooks99: Hooks MA, Kellas F, Graham IA (1999). "Long-chain acyl-CoA oxidases of Arabidopsis." Plant J 20(1);1-13. PMID: 10571860

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

Showing only 20 references. To show more, press the button "Show all references".

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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