Nicotine Pathway Map

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This pathway was contributed by Ben Vickers, Meaghan Fitzgerald, Sean Anderson, Lynda Ellis and Michael Turnbull, University of Minnesota.

Nicotine is the primary alkaloid found in tobacco plants. Nearly everyone knows that it causes the addictive nature of cigarettes, cigars and snuff - some still experience this first hand. Less known is that nicotine, under the names Nico-Fume, Black Leaf 40 (a 40% solution of nicotine), Tendust and others, can be used as an insecticide. This practice is rare within the United States yet much is still sold outside the US for this purpose.

In Arthrobacter nicotinovorans (Grether-Beck et al., 1994) and Arthrobacter oxydans (Gherna et al., 1965), nicotine is converted to both (S)-6-Hydroxynicotine and (R)-6-Hydroxynicotine by nicotine dehydrogenase. Stereospecific enzymes (S)-6-hydroxynicotine oxygenase and (R)-6-hydroxynicotine oxygenase catalyze the formation of 6-hydroxypseudooxynicotine which is degraded through 2,6-dihydroxypyridine (Grether-Beck et al., 1994).

Pseudomonas sp. strains P-34 and JTS-006 convert 6-hydroxypseudooxynicotine to 6-hydroxy-3-succinoylpyridine, which forms 2,5- (rather than 2,6-) dihydroxypyridine (Gherna et al., 1965). Pseudomonas putida biotype A strain S16 uses a varient of this pathway. It delays 6-hydroxylation of the aromatic ring until the formation of 3-succinoylpyridine. This is hydroxylated to form 6-hydroxy-3-succinoylpyridine, and the remaining pathway for that is as shown here (Wang et al., 2007).

The three end products of this degradation as shown here are Maleamate, 4-Aminobutyrate, and 2,6-Dihydroxy-N-methylmyosmine. The metabolism of Maleamate and 4-Aminobutyrate continue through regular microbial channels. 2,6-Dihydroxy-N-methylmyosmine formed spontaneously from 2,6-Dihydroxypseudooxynicotine is reported as metabolically inactive in this species.

Organisms which can initiate the pathway are given, but other organisms may also carry out later steps. Follow the links for more information on compounds or reactions. This map is also available in a graphic (15k) format.

                                        (RS)-Nicotine
Arthrobacter nicotinovorans
plasmid pAO1
Arthrobacter oxydans
|
|
+-------+-------+
| |
nicotine | | nicotine
dehydrogenase | | dehydrogenase
| |
v v
(S)-6-Hydroxy- (R)-6-Hydroxy-
nicotine nicotine
| |
(S)-6-hydroxynicotine | | (R)-6-hydroxynicotine
oxygenase | | oxygenase
| |
v v
6-Hydroxypseudooxynicotine ------------+
| | Pseudomonas sp. P-34 and JTS-0006
| 6-hydroxypseudo- |
| oxynicotine | 6-hydroxy-
| monooxygenase v pseudooxynicotine
| | dehydrogenase
spontaneous v |
2,6-Dihydroxy- <-------------- 2,6-Dihydroxypseudooxynicotine |
N-methylmyosmine | |
| 2,6-dihydroxy- v
| pseudo- 6-Hydroxy-
| oxynicotine 3-succinoylpyridine
| hydrolase |
| |
+-------------------------------+ | 6-hydroxy-
| | | 3-succinoyl-
| | | pyridine
v v | hydrolase
2,6-Dihydroxypyridine 4-Methylaminobutyrate |
| | | |
2,6-dihydroxy- | 4-methylamino- | | v
pyridine | butanoate oxidase | | Succinic semialdehyde + 2,5-Dihydroxypyridine
oxidase | | | | |
| | | 4-methylamino- | |
v v | butanoate | succinic semialdehyde |
2,3,6-Trihydroxypyridine 4-Aminobutanoate | oxidase | dehydrogenase | 2,5-dihydroxy-
| | | (methylamine- | | pyridine
B v | | forming) v | 5,6-dioxygenase
| v +------------> Succinate |
| Intermediary | |
v Metabolism | v
Maleamate <-----------+ (KEGG) v N-Formyl-
| | Intermediatry maleamate
| | Metabolism |
v | (KEGG) |
Intermediary | N-formylmaleamate deformylase |
Metabolism +---------------------------------------------------------------+
(KEGG)



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Page Author(s): Ben Vickers, Meaghan Fitzgerald, Sean Anderson, Lynda Ellis and Michael Turnbull

April 17, 2013 Contact Us

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