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:||Degradation/Utilization/Assimilation → Amino Acids Degradation → Proteinogenic Amino Acids Degradation → L-tryptophan Degradation|
Expected Taxonomic Range:
A new L-tryptophan catabolic pathway has been described in the bacterium Burkholderia cenocepacia J2315. In this pathway, L-tryptophan is converted to aminocarboxymuconate semialdehyde, which is enzymatically degraded to pyruvate and acetyl-CoA via the intermediates 2-aminomuconate and 4-oxaloisocrotonate, a route that is commonly used by bacteria for the degradation of nitroaromatic compounds [Colabroy05]. Several of the enzymes have been cloned and overexpressed, and their activity verified (these enzymes include 3-hydroxyanthranilate 3,4-dioxygenase, aminocarboxymuconate-semialdehyde decarboxylase, 2-aminomuconate semialdehyde dehydrogenase and 2-aminomuconate deaminase). Other enzymes in this pathway are predicted, based on the presence of putative genes encoding them in the same gene clusters that include the verifed enzymes. Such predicted enzymes include 4-oxalocrotonate decarboxylase (EC 220.127.116.11), 2-ket-pentenoate hydratase (EC 18.104.22.168), 2-keto-4-hydroxypentenoate aldolase, and acetaldehyde dehydrogenase. These genes are found in two clusters in Burkholderia cenocepacia J2315, but were found in a single uninterrupted cluster in Bacillus cereus 10897, supporting the notion of a shared metabolic function of these genes in tryptophan metabolism [Colabroy05]. Putative genes encoding the first three reactions in the pathway were also found in the Burkholderia cenocepacia J2315 genome. However, no gene encoding kynurenine-3-monooxygenase (EC 22.214.171.124) was found, suggesting that the reaction is catalyzed by a nonorthologous form of the enzyme in this organism.
This pathway shares the upstream set of reactions (up to 2-aminomuconate) with the tryptophan degradation pathway that is proposed to operate in mammals (see L-tryptophan degradation III (eukaryotic)). However, the downstream part of the pathway differs from the mammalian pathway, in which aminocarboxymuconate semialdehyde is converted via completely different intermediates, which include 2-oxoadipate and glutaryl-CoA.
Variants: L-tryptophan degradation I (via anthranilate), L-tryptophan degradation II (via pyruvate), L-tryptophan degradation III (eukaryotic), L-tryptophan degradation IV (via indole-3-lactate), L-tryptophan degradation V (side chain pathway), L-tryptophan degradation VI (via tryptamine), L-tryptophan degradation VII (via indole-3-pyruvate), L-tryptophan degradation VIII (to tryptophol), L-tryptophan degradation X (mammalian, via tryptamine), L-tryptophan degradation XI (mammalian, via kynurenine), L-tryptophan degradation XII (Geobacillus)
AlberatiGiani97: Alberati-Giani D, Cesura AM, Broger C, Warren WD, Rover S, Malherbe P (1997). "Cloning and functional expression of human kynurenine 3-monooxygenase." FEBS Lett 410(2-3);407-12. PMID: 9237672
Austin09: Austin CJ, Astelbauer F, Kosim-Satyaputra P, Ball HJ, Willows RD, Jamie JF, Hunt NH (2009). "Mouse and human indoleamine 2,3-dioxygenase display some distinct biochemical and structural properties." Amino Acids 36(1);99-106. PMID: 18274832
Basran08: Basran J, Rafice SA, Chauhan N, Efimov I, Cheesman MR, Ghamsari L, Raven EL (2008). "A kinetic, spectroscopic, and redox study of human tryptophan 2,3-dioxygenase." Biochemistry 47(16);4752-60. PMID: 18370401
Breton00: Breton J, Avanzi N, Magagnin S, Covini N, Magistrelli G, Cozzi L, Isacchi A (2000). "Functional characterization and mechanism of action of recombinant human kynurenine 3-hydroxylase." Eur J Biochem 267(4);1092-9. PMID: 10672018
Calderone02: Calderone V, Trabucco M, Menin V, Negro A, Zanotti G (2002). "Cloning of human 3-hydroxyanthranilic acid dioxygenase in Escherichia coli: characterisation of the purified enzyme and its in vitro inhibition by Zn2+." Biochim Biophys Acta 1596(2);283-92. PMID: 12007609
Ferrandez97: Ferrandez A, Garcia JL, Diaz E (1997). "Genetic characterization and expression in heterologous hosts of the 3-(3-hydroxyphenyl)propionate catabolic pathway of Escherichia coli K-12." J Bacteriol 1997;179(8);2573-81. PMID: 9098055
Fischer13: Fischer B, Boutserin S, Mazon H, Collin S, Branlant G, Gruez A, Talfournier F (2013). "Catalytic properties of a bacterial acylating acetaldehyde dehydrogenase: evidence for several active oligomeric states and coenzyme A activation upon binding." Chem Biol Interact 202(1-3);70-7. PMID: 23237860
Fukuoka02: Fukuoka S, Ishiguro K, Yanagihara K, Tanabe A, Egashira Y, Sanada H, Shibata K (2002). "Identification and expression of a cDNA encoding human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD). A key enzyme for the tryptophan-niacine pathway and "quinolinate hypothesis"." J Biol Chem 277(38);35162-7. PMID: 12140278
Gupta00: Gupta S, Mat-Jan F, Latifi M, Clark DP (2000). "Acetaldehyde dehydrogenase activity of the AdhE protein of Escherichia coli is inhibited by intermediates in ubiquinone synthesis." FEMS Microbiol Lett 182(1);51-5. PMID: 10612730
Harayama89: Harayama S, Rekik M, Ngai KL, Ornston LN (1989). "Physically associated enzymes produce and metabolize 2-hydroxy-2,4-dienoate, a chemically unstable intermediate formed in catechol metabolism via meta cleavage in Pseudomonas putida." J Bacteriol 171(11);6251-8. PMID: 2681159
Hasegawa00: Hasegawa Y, Muraki T, Tokuyama T, Iwaki H, Tatsuno M, Lau PC (2000). "A novel degradative pathway of 2-nitrobenzoate via 3-hydroxyanthranilate in Pseudomonas fluorescens strain KU-7." FEMS Microbiol Lett 190(2);185-90. PMID: 11034277
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