The enzymes of microbial nicotine metabolism

Abstract

Because of nicotine's toxicity and the high levels found in tobacco and in the waste from tobacco processing, there is a great deal of interest in identifying bacteria capable of degrading it. A number of microbial pathways have been identified for nicotine degradation. The first and best-understood is the pyridine pathway, best characterized for Arthrobacter nicotinovorans, in which the first reaction is hydroxylation of the pyridine ring. The pyrrolidine pathway, which begins with oxidation of a carbon-nitrogen bond in the pyrrolidine ring, was subsequently characterized in a number of pseudomonads. Most recently, a hybrid pathway has been described, which incorporates the early steps in the pyridine pathway and ends with steps in the pyrrolidine pathway. This review summarizes the present status of our understanding of these pathways, focusing on what is known about the individual enzymes involved.

Keywords: biodegradation; enzyme mechanism; flavoprotein; metabolic pathway; nicotine.

Scheme 1

Nicotine catabolism in A. nicotinovorans. The respective gene names are given in parentheses.

Scheme 2

Hydroxylation of nicotine by the molybdopterin cofactor of nicotine dehydrogenase.

Figure 1

Overlay of the structure of LHNO (blue, pdb file 3NG7) with that of human MAO B (orange, pdb file 2FXU). The bound 6-hydroxynicotine is shown with green carbons.

Scheme 3

Proposed mechanism of LHNO [21].

Scheme 4

Mechanism of LHNO.

Figure 2

Overlay of the structures of DHNO (blue, pdb file 2bvf) and tirandamycin oxidase (orange, pdb file 2y3s), another member of the p-cresol methylhydroxylase/vanillyl oxidase family. The carbon atoms of tirandamycin are in green.

Scheme 5

Proposed mechanism for DHNO [27].

Scheme 6

Mechanism of 2,6-dihydroxypseudooxynicotine hydrolase [37].

Figure 3

Overlay of structures of salicylate hydroxylase (orange, pdb file 5evy) and 2,3-dihydroxypyridine 3-hydroxylase (blue, pdb file 2vou). The salicylate bound to the latter is shown in green.

Scheme 7

Mechanism of 2,3-dihydroxypyridine 3-hydroxylase [42].

Scheme 8

The pyrrolidine pathway for nicotine degradation by pseudomonads. The gene names for P. putida S16 (black), P. putida J5 (red), and Pseudomonas sp. HZN6 (blue) are in parentheses.

Figure 4

Overlay of the structure of LHNO (magenta, pdb file 3NG7) with that of NicA2 (magenta, pdb file 5ttj) B (green, pdb file 2FXU). The bound 6-hydroxynicotine is shown with green carbons.

Scheme 9

The pseudooxynicotine amine oxidase reaction.

Scheme 10

Mechanism of HspB [59].

Scheme 11

Hybrid pyridine/pyrrolidine pathway for nicotine metabolism in Agrobacter tumefaciens S33 (black), Ochrobactrum sp. SJY1 (red), and Sphingomonas melonis Ty (blue).