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MetaCyc Pathway: L-tryptophan degradation I (via anthranilate)
Inferred from experiment

Enzyme View:

Pathway diagram: L-tryptophan degradation I (via anthranilate)

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.

Synonyms: anthranilate pathway

Superclasses: Degradation/Utilization/AssimilationAmino Acids DegradationProteinogenic Amino Acids DegradationL-tryptophan Degradation

Some taxa known to possess this pathway include : Acinetobacter, Bacillus anthracis, Bacillus cereus, Bacillus megaterium, Bordetella pertussis, Burkholderia cepacia, Burkholderia xenovorans LB400, Cupriavidus metallidurans CH34, Delftia acidovorans, Pseudomonas aeruginosa, Pseudomonas chlororaphis chlororaphis, Pseudomonas fluorescens, Ralstonia solanacearum, Streptomyces parvulus, Thermobifida fusca, Xanthobacter, Xanthomonas arboricola

Expected Taxonomic Range: Bacteria

The aerobic degradation of L-tryptophan by eukaryotes, often referred to as the kynurenine pathway, is the major route of L-tryptophan degradation in mammals (see L-tryptophan degradation III (eukaryotic)). The enzymology of the kynurenine pathway in humans and in yeasts has been largely elucidated over the last 20 years, and the genes for most of the enzymes have been identified. In contrast, a lot less is known about the aerobic degradation of L-tryptophan in bacteria. It was shown early on that certain unidentified Pseudomonads could oxidize tryptophan to catechol through kynurenine and anthranilate [Stanier51]. In some species of Pseudomonadaceae and Bacillaceae the oxidative degradation of exogenous L-tryptophan was implicated as a sole source of carbon and nitrogen [Bouknight75, Hamill70, Nozaki72].

Tryptophan 2,3-dioxygenase (TDO; EC, activity has been described in some bacteria [Eguchi84], but no corresponding genes have been identified until recently. The fact that some bacteria can degrade kynurenine further suggested the presence of two additional enzymes, kynurenine formamidase and kynureninase. Based on sequence similarity to eukaryotic genes, the gene encoding kynureninase (KYN; EC was cloned from Pseudomonas fluorescens [Koushik97], and the corresponding enzyme was characterized in detail [Phillips98]. Later, similarity to eukaryotic sequences revealed the bacterial gene encoding tryptophan dioxygenase in several bacteria [Kurnasov03]. Finally, chromosomal gene clustering analysis revealed the presence of the third gene, encoding kynurenine formamidase (EC in an operon including the other two genes [Kurnasov03]. This functional prediction was experimentally verified by cloning, expression and enzymatic characterization of recombinant kynurenine formamidase orthologs from Bacillus cereus, Pseudomonas aeruginosa and Cupriavidus metallidurans CH34. In addition, functional expression in Escherichia coli of the Cupriavidus metallidurans CH34 putative kynBAU operon encoding all three genes confirmed the function of this operon [Kurnasov03].

Superpathways: L-tryptophan degradation XII (Geobacillus), superpathway of aromatic compound degradation via 2-oxopent-4-enoate, superpathway of aromatic compound degradation via 3-oxoadipate

Variants: L-tryptophan degradation II (via pyruvate), L-tryptophan degradation III (eukaryotic), L-tryptophan degradation IV (via indole-3-lactate), L-tryptophan degradation VII (via indole-3-pyruvate), L-tryptophan degradation VIII (to tryptophol), L-tryptophan degradation IX, L-tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde, L-tryptophan degradation V (side chain pathway), L-tryptophan degradation VI (via tryptamine), L-tryptophan degradation X (mammalian, via tryptamine), L-tryptophan degradation XI (mammalian, via kynurenine)

Created 11-Aug-1998 by Ying HC, SRI International
Revised 21-Mar-2005 by Caspi R, SRI International


Bouknight75: Bouknight RR, Sadoff HL (1975). "Tryptophan catabolism in Bacillus megaterium." J Bacteriol 121(1);70-6. PMID: 803956

Eguchi84: Eguchi N, Watanabe Y, Kawanishi K, Hashimoto Y, Hayaishi O (1984). "Inhibition of indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase by beta-carboline and indole derivatives." Arch Biochem Biophys 232(2);602-9. PMID: 6431906

Hamill70: Hamill RL, Elander RP, Mabe JA, Gorman M (1970). "Metabolism of tryptophan by Pseudomonas aureofaciens. 3. Production of substituted pyrrolnitrins from tryptophan analogues." Appl Microbiol 19(5);721-5. PMID: 4316270

Koushik97: Koushik SV, Sundararaju B, McGraw RA, Phillips RS (1997). "Cloning, sequence, and expression of kynureninase from Pseudomonas fluorescens." Arch Biochem Biophys 344(2);301-8. PMID: 9264543

Kurnasov03: Kurnasov O, Jablonski L, Polanuyer B, Dorrestein P, Begley T, Osterman A (2003). "Aerobic tryptophan degradation pathway in bacteria: novel kynurenine formamidase." FEMS Microbiol Lett 227(2);219-27. PMID: 14592712

Nozaki72: Nozaki M, Ishimura Y (1972). "Tryptophan metabolism in micro-organisms." Biochem J 128(1);24P-25P. PMID: 4628622

Phillips98: Phillips RS, Sundararaju B, Koushik SV (1998). "The catalytic mechanism of kynureninase from Pseudomonas fluorescens: evidence for transient quinonoid and ketimine intermediates from rapid-scanning stopped-flow spectrophotometry." Biochemistry 37(24);8783-9. PMID: 9628740

Stanier51: Stanier RY, Hayaishi O, Tsuchida M (1951). "The bacterial oxidation of tryptophan. I. A general survey of the pathways." J Bacteriol 62(4);355-66. PMID: 14897807

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

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

Batabyal07: Batabyal D, Yeh SR (2007). "Human tryptophan dioxygenase: a comparison to indoleamine 2,3-dioxygenase." J Am Chem Soc 129(50);15690-701. PMID: 18027945

Brady75: Brady FO (1975). "Tryptophan 2,3-dioxygenase: a review of the roles of the heme and copper cofactors in catalysis." Bioinorg Chem 5(2);167-82. PMID: 178384

Brown86: Brown D, Hitchcock MJ, Katz E (1986). "Purification and characterization of kynurenine formamidase activities from Streptomyces parvulus." Can J Microbiol 32(6);465-72. PMID: 2425918

Hitchcock88: Hitchcock MJ, Katz E (1988). "Purification and characterization of tryptophan dioxygenase from Streptomyces parvulus." Arch Biochem Biophys 261(1);148-60. PMID: 3341771

Keller10: Keller U, Lang M, Crnovcic I, Pfennig F, Schauwecker F (2010). "The actinomycin biosynthetic gene cluster of Streptomyces chrysomallus: a genetic hall of mirrors for synthesis of a molecule with mirror symmetry." J Bacteriol 192(10);2583-95. PMID: 20304989

Kurnasov03a: Kurnasov O, Goral V, Colabroy K, Gerdes S, Anantha S, Osterman A, Begley TP (2003). "NAD biosynthesis: identification of the tryptophan to quinolinate pathway in bacteria." Chem Biol 10(12);1195-204. PMID: 14700627

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lima07: Lima S, Khristoforov R, Momany C, Phillips RS (2007). "Crystal structure of Homo sapiens kynureninase." Biochemistry 46(10);2735-44. PMID: 17300176

Littlejohn03: Littlejohn TK, Takikawa O, Truscott RJ, Walker MJ (2003). "Asp274 and his346 are essential for heme binding and catalytic function of human indoleamine 2,3-dioxygenase." J Biol Chem 278(32);29525-31. PMID: 12766158

Matsumura84: Matsumura M, Osada K, Aiba S (1984). "L-tryptophan 2,3-dioxygenase of a moderate thermophile, Bacillus brevis. Purification, properties and a substrate-mediated stabilization of the quaternary structure." Biochim Biophys Acta 786(1-2);9-17. PMID: 6712960

Momany04: Momany C, Levdikov V, Blagova L, Lima S, Phillips RS (2004). "Three-dimensional structure of kynureninase from Pseudomonas fluorescens." Biochemistry 43(5);1193-203. PMID: 14756555

Pabarcus05: Pabarcus MK, Casida JE (2005). "Cloning, expression, and catalytic triad of recombinant arylformamidase." Protein Expr Purif 44(1);39-44. PMID: 15935693

Panozzo02: Panozzo C, Nawara M, Suski C, Kucharczyka R, Skoneczny M, Becam AM, Rytka J, Herbert CJ (2002). "Aerobic and anaerobic NAD+ metabolism in Saccharomyces cerevisiae." FEBS Lett 517(1-3);97-102. PMID: 12062417

Poillon69: Poillon WN, Maeno H, Koike K, Feigelson P (1969). "Tryptophan oxygenase of Pseudomonas acidovorans. Purification, composition, and subunit structure." J Biol Chem 244(13);3447-56. PMID: 4307451

Rafice09: Rafice SA, Chauhan N, Efimov I, Basran J, Raven EL (2009). "Oxidation of L-tryptophan in biology: a comparison between tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase." Biochem Soc Trans 37(Pt 2);408-12. PMID: 19290871

Shimizu78: Shimizu T, Nomiyama S, Hirata F, Hayaishi O (1978). "Indoleamine 2,3-dioxygenase. Purification and some properties." J Biol Chem 253(13);4700-6. PMID: 26687

Takeuchi80: Takeuchi F, Otsuka H, Shibata Y (1980). "Purification and properties of kynureninase from rat liver." J Biochem 88(4);987-94. PMID: 7451426

Toma97: Toma S, Nakamura M, Tone S, Okuno E, Kido R, Breton J, Avanzi N, Cozzi L, Speciale C, Mostardini M, Gatti S, Benatti L (1997). "Cloning and recombinant expression of rat and human kynureninase." FEBS Lett 408(1);5-10. PMID: 9180257

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
Page generated by Pathway Tools version 19.5 (software by SRI International) on Sat Apr 30, 2016, biocyc14.