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MetaCyc Pathway: nicotinate degradation I
Inferred from experiment

Enzyme View:

Pathway diagram: nicotinate degradation I

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: maleamate pathway, nicotinate degradation

Superclasses: Degradation/Utilization/AssimilationAromatic Compounds DegradationNicotinate Degradation

Some taxa known to possess this pathway include : Bordetella bronchiseptica RB50, Pseudomonas fluorescens, Pseudomonas fluorescens ATCC 23728, Pseudomonas fluorescens TN5, Pseudomonas putida, Pseudomonas putida KT2440, Pseudomonas putida N-9

Expected Taxonomic Range: Proteobacteria

Nicotinate (niacin, 3-pyridinecarboxylate) is a carboxylic derivative of pyridine that is found in nature as part of pyridine cofactors (e.g., NAD and NADP) and alkaloids (e.g., (S)-nicotine and anabasine). Nicotinate is an essential compound for those organisms that are not able to synthesize it, and is thus also called vitamin B3. In addition, nicotinate is also a carbon and nitrogen source for different bacteria and some fungi.

Microorganisms have multiple ways of degrading pyridine and its derivatives, and degradation of these compounds is relevant to both biological and industrial processes. The degradation of nicotinate by both aerobic and anaerobic organisms involves the initial formation of 6-hydroxynicotinate, but the pathways diverge after that. This pathway describes the degradation of nicotinate as performed by the aerobic bacteria Pseudomonas fluorescens and Pseudomonas putida.

The pathway was originally studied in several strains of Pseudomonas putida and Pseudomonas fluorescens, such as Pseudomonas fluorescens TN5 and Pseudomonas putida N-9 [Behrman57, Gauthier71]. The segment of the pathway beginning with 2,5-dihydroxypyridine has also been shown in two strains of Achromobacter sp. grown on 2-hydroxypyridine or 3-hydroxypyridine [Cain74, Houghton72].

A much more recent study of Pseudomonas putida KT2440 identified the genetic determinants of the pathway [Jimenez08]. This study also found that the conversion of 2,5-dihydroxypyridine to maleamate is a two step process via N-formylmaleamate, catalyzed by two distinct enzymes, encoded by nicX and nicD, and not a single step as was assumed until then.

The pathway starts with two hydroxylation reactions. The first enzyme, nicotinate dehydrogenase (cytochrome), derives the oxygen from water, rather than molecular oxygen. The Pseudomonas enzyme is unusual in having three c-type cytochromes rather than FAD, which is the usual cofactor of enzymes in this family. The cytochromes enable the enzyme to interact directly with respiratory chain, most likely transferring the electrons to an oxygen-dependent terminal oxidase [Hunt58, Jimenez08, Yang09]. The second hydroxylation is catalyzed by 6-hydroxynicotinate 3-monooxygenase, a dioxygen-dependent enzyme.

The next reaction, catalyzed by the nicX-encoded 2,5-dihydroxypyridine dioxygenase, cleaves the ring structure. Following a deformylation to maleamate, a maleamate amidohydrolase enzyme catalyzes hydrolytic deamination, a step that liberates ammonium and enables nicotinate to serve as a sole nitrogen source for the organisms.

The final reaction of the pathway is isomerization to fumarate, a TCA cycle intermediate [Behrman57, Kaiser96].

Superpathways: superpathway of nicotinate degradation

Variants: nicotinate degradation II, nicotinate degradation III

Created 03-May-2001 by Pellegrini-Toole A, Marine Biological Laboratory
Revised 25-Mar-2010 by Caspi R, SRI International


Behrman57: Behrman, E.J., Stanier, R.Y. (1957). "The bacterial oxidation of nicotinic acid." J Biol Chem 228(2);923-45. PMID: 13475371

Cain74: Cain RB, Houghton C, Wright KA (1974). "Microbial metabolism of the pyridine ring. Metabolism of 2- and 3-hydroxypyridines by the maleamate pathway in Achromobacter sp." Biochem J 1974;140(2);293-300. PMID: 4455192

Gauthier71: Gauthier JJ, Rittenberg SC (1971). "The metabolism of nicotinic acid. I. Purification and properties of 2,5-dihydroxypyridine oxygenase from Pseudomonas putida N-9." J Biol Chem 246(11);3737-42. PMID: 5578917

Houghton72: Houghton C, Cain RB (1972). "Microbial metabolism of the pyridine ring. Formation of pyridinediols (dihydroxypyridines) as intermediates in the degradation of pyridine compounds by micro-organisms." Biochem J 130(3);879-93. PMID: 4664939

Hunt58: Hunt, A.L., Hughes, D.E., Lowenstein, J.M. (1958). "The hydroxylation of nicotinic acid by Pseudomonas fluorescens." Biochem J 69(2);170-3. PMID: 13546162

Jimenez08: Jimenez JI, Canales A, Jimenez-Barbero J, Ginalski K, Rychlewski L, Garcia JL, Diaz E (2008). "Deciphering the genetic determinants for aerobic nicotinic acid degradation: the nic cluster from Pseudomonas putida KT2440." Proc Natl Acad Sci U S A 105(32);11329-34. PMID: 18678916

Kaiser96: Kaiser JP, Feng Y, Bollag JM (1996). "Microbial metabolism of pyridine, quinoline, acridine, and their derivatives under aerobic and anaerobic conditions." Microbiol Rev 60(3);483-98. PMID: 8840783

Yang09: Yang Y, Yuan S, Chen T, Ma P, Shang G, Dai Y (2009). "Cloning, heterologous expression, and functional characterization of the nicotinate dehydrogenase gene from Pseudomonas putida KT2440." Biodegradation 20(4);541-9. PMID: 19118407

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

Chen13: Chen D, Tang H, Lv Y, Zhang Z, Shen K, Lin K, Zhao YL, Wu G, Xu P (2013). "Structural and computational studies of the maleate isomerase from Pseudomonas putida S16 reveal a breathing motion wrapping the substrate inside." Mol Microbiol 87(6);1237-44. PMID: 23347155

Gauthier71a: Gauthier JJ, Rittenberg SC (1971). "The metabolism of nicotinic acid. II. 2,5-dihydroxypyridine oxidation, product formation, and oxygen 18 incorporation." J Biol Chem 246(11);3743-8. PMID: 5578918

Hatakeyama00: Hatakeyama K, Goto M, Kobayashi M, Terasawa M, Yukawa H (2000). "Analysis of oxidation sensitivity of maleate cis-trans isomerase from Serratia marcescens." Biosci Biotechnol Biochem 64(7);1477-85. PMID: 10945267

Hatakeyama97: Hatakeyama K, Asai Y, Uchida Y, Kobayashi M, Terasawa M, Yukawa H (1997). "Gene cloning and characterization of maleate cis-trans isomerase from Alcaligenes faecalis." Biochem Biophys Res Commun 239(1);74-9. PMID: 9345272

Hurh94: Hurh B, Yamane T, Nagasawa T (1994). "Purification and characterization of nicotinic acid dehydrogenase from Pseudomonas fluorescens TN5." J. Ferment. Bioeng. 78, No. 1, 19-26.

Kincaid12: Kincaid VA, Sullivan ED, Klein RD, Noel JW, Rowlett RS, Snider MJ (2012). "Structure and Catalytic Mechanism of Nicotinate (Vitamin B(3)) Degradative Enzyme Maleamate Amidohydrolase from Bordetella bronchiseptica RB50." Biochemistry 51(1);545-54. PMID: 22214383

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

Munn86: Munn C A M (1886). "Researches on Myohaematin and the Histohaematins." Philosophical Transactions of the Royal Society of London 177(0);267-298.

Nakano99: Nakano H, Wieser M, Hurh B, Kawai T, Yoshida T, Yamane T, Nagasawa T (1999). "Purification, characterization and gene cloning of 6-hydroxynicotinate 3-monooxygenase from Pseudomonas fluorescens TN5." Eur J Biochem 260(1);120-6. PMID: 10091591

Scher69: Scher W, Jakoby WB (1969). "Maleate isomerase." J Biol Chem 244(7);1878-82. PMID: 5780844

Silby09: Silby MW, Cerdeno-Tarraga AM, Vernikos GS, Giddens SR, Jackson RW, Preston GM, Zhang XX, Moon CD, Gehrig SM, Godfrey SA, Knight CG, Malone JG, Robinson Z, Spiers AJ, Harris S, Challis GL, Yaxley AM, Harris D, Seeger K, Murphy L, Rutter S, Squares R, Quail MA, Saunders E, Mavromatis K, Brettin TS, Bentley SD, Hothersall J, Stephens E, Thomas CM, Parkhill J, Levy SB, Rainey PB, Thomson NR (2009). "Genomic and genetic analyses of diversity and plant interactions of Pseudomonas fluorescens." Genome Biol 10(5);R51. PMID: 19432983

Tang12: Tang H, Yao Y, Wang L, Yu H, Ren Y, Wu G, Xu P (2012). "Genomic analysis of Pseudomonas putida: genes in a genome island are crucial for nicotine degradation." Sci Rep 2;377. PMID: 22530095

Yu15: Yu H, Tang H, Zhu X, Li Y, Xu P (2015). "Molecular mechanism of nicotine degradation by a newly isolated strain, Ochrobactrum sp. strain SJY1." Appl Environ Microbiol 81(1);272-81. PMID: 25344232

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, biocyc13.