Nornicotine biosynthesis

Lewis RS, Bowen SW, Keogh MR, Dewey RE (2010) Three nicotine demethylase genes mediate nornicotine biosynthesis in Nicoticma tabacum L. functional characterization of the CYP82E10 gene. Phytochemistry 71 1988-1998... 

The overexpression of both trl and h6h from H. niger in N. tabacum plants have been reported [160]. Here, transgenic and control tobacco plants were fed with the tropane intermediate tropinone. Thus, tropine, the TRI-reaction product, was detected only in leaves of transgenic plants, with no correlation with trl transcript level and tropine amounts. Surprisingly, transgenic tobacco plants contained 3 to 13-fold more nicotine than wild type plants. Also, the presence of considerable amounts of nornicotine, myosmine, anabasine and anatabine contrasted with low levels in wild-type plants, indicating that the overexpression of trl and h6h perturb the normal nicotine biosynthesis when these new genes taken from a different metabolic pathway are introduced in tobacco [160]. 

For studies on the interrelationsship among nicotine, nornicotine, anabasine and anatabine during the biosynthesis in Nicotiana glutinosa, Alworth and Rapoport used almost the same gas chromatographic conditions as reported above. On a polybutylene glycol column the alkaloids mentioned were satisfactorily resolved. 

There is an alternative way of viewing the above results, however. It could be that the biosynthetic pathway to the pyrrolidine ring of nicotine is similar (in part) to the route to the piperidine alkaloids. Part of the model suggested for the biosynthesis of the piperidine nucleus from lysine (see above) could be easily adapted to account for the C02 and nornicotine results, that is variable/in-complete equilibration of bound putrescine (arising by enzyme-mediated decarboxylation of ornithine) with unbound material. L-Ornithine decarboxylase (EC 4.1.1.17, L-ornithine carboxy-lyase) occurs widely in higher plants and like L-lysine decarboxylase requires pyridoxal phosphate as a co-factor. ... 

Figure 2.6a. Biosynthesis of anabasine, nicotine, and nornicotine from a common substrate, nicotinic acid, in Nicotiana glauca (pathway B) and in N. tabacum (pathway B ).

The formation of nicotinic acid—or, more precisely, of quinolinic acid—via two different pathways is an example of biochemical convergence, Now to the biosynthesis of the pyrrolidine ring of nicotine and nornicotine. Ornithine comes into play here. It furnishes the pyrrolidine component by the route already outlined, and this is then combined with nicotinic acid to give nicotine (Fig. 124). It is not known with certainty at what stage the methyl group is introduced. Very probably ornithine or putrescine is methylated and the methylated precursor is then icorporated into nicotine. Nicotine can be converted into nornicotine by demethyla-tion. 

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