Alkaloid production

Kirch et al. (1995) examined individual plants collected in Corsica, Elba, Sardinia, Liguria, and Provence for alkaloids and observed four groups, one characterized by sparteine [119] (see Fig. 2.34 for structures 119-124), one characterized by lupanine-based alkaloids [120 and 121], one that had a very low level of alkaloid production, and one that lacked sparteine and lupanine-based compounds, but did accumulate other alkaloids such as anagyrine [122], ammodendrine [123], and compounds based on cytisine [124], their outlier group. The distribution of these four chemotypes is presented in Table 2.10. 

Taber, W. A. Ergot alkaloid Production and Physiology of Claviceps purpurea (Fr.) Tul. Developments in Industrial Microbiology 4, 295 (1963). 

The effect of light on alkaloid production in these cultures was also evaluated (7/9). More catharanthine was produced in the light than in the dark, and the same observation was made for ajmalicine (39). Knobloch et al. 120) examined the production of anthocyanins, ajmalicine (39), and serpentine (40) in cell suspension cultures and found that although serpentine levels increased 18-fold in the light, ajmalicine levels decreased 50%. In the work of Goodbody et al. 119) the biosynthesis of vindoline (3)... 

The effect of phosphate on alkaloid production has also been evaluated (138). Using a modified induction medium devoid of phosphate and other essential growth factors, production of secondary compounds was more rapid than when phosphate was present. A broader study of the phenomenon has been reported by a French group (139) where, using three alkaloids as markers, the disappearance of the major nutrients from the medium and the evolution of phosphates, nitrates, ammonium ions, glucose, and starch in the cells were observed over time. It was not possible to relate alkaloid accumulation to the appearance or disappearance of any one metabolite in particular. However, other workers have found that the rate of biomass accumulation was directly related to the rate of formation of cellular serpentine (40) (140). 

Kreuger and Carew (141) examined the effects of a number of alkaloid precursors on alkaloid production in suspension cultures and found that at 100 mg/liter tryptamine hydrochloride enhanced alkaloid production. The alkaloids produced, however, were A-acetyltryptamine and N,N-dimethyltryptamine, rather than the monoterpenoid indole alkaloids. Added geraniol and mevalonic acid had no effect on alkaloid production. 

The conversion of anhydrovinblastine (8) to vinblastine (1) has been examined by several different groups, using intact plants, cell suspension systems, and cell-free preparations. From the studies discussed above it was clear that 3, 4 -anhydrovinblastine (8) was probably the initially formed intermediate in the condensation of vindoline (3) and catharanthine (4) prior to vinblastine (1). Kutney and co-workers have reported (225,226) on the biotransformation of 3, 4 -anhydrovinblastine (8) using cell suspension cultures of the 916 cell line from C. roseus a line which did not produce the normal spectrum of indole alkaloids. After 24 hr the major alkaloid products were leurosine (11) and Catharine (10) in 31 and 9% yields, respectively, with about 40% of the starting alkaloid consumed. 

A few novel N-containing and alkaloid products have been isolated from dicot plant endophytes recently. Although not nearly as numerous as the hydrocarbon products, the implications of some of these compounds are significant. Simplest among the amino and amide compounds are 3-nitropropionic acid (NPA)(167) and indole-3-acetic acid (IAA)(168). NPA is isolated frequently from plant tissues and it has significant biological activity. Chomcheon et isolated... 

Figure 96. Diagram of alkaloid production by cell culture. Abbreviations A - alkaloid synthesis.

The hybrid is able to produce more alkaloids than the basic callus, which is an undifferentiated mass of cells. Alkaloid production in cell cultures can be more successful with the immobihzation of plant cells and enzymes and by using bioreactor systems . Alkaloid produced in cell cultures can be isolated directly from this culture or from young plants grown from this culture. More than 250 alkaloids are reported to be produced by cell-culture techniques. Only a limited number of species have been researched in this respect. The species studied are known to produce alkaloids with special use in applications. The most researched alkaloids produced by cell cultures are mentioned in Table 25. 

Williams, W., Harrison, J. E. M. and Jayasekera, S. 1984. Genetic control of alkaloid production in Lupinus mutabilis on the effect of a mutant alle mutal isolated following chemical mutagenesis. Euphytica, 33 811-817. 

Anderson, L. A., Phillipson, J. D. and Roberts, M. F. 1987. Alkaloid production by plant cells. In Plant and Animal Cell Cultures, Process, Possibilities (Webb, C. and Mavituna, F. eds.), pp. 172-192. Chichester Ellis Horwood. 

Sauerwein, M. and Shimomura, K. 1991. Alkaloid production in hairy roots of Hyoscyamus albus transformed with Agrobacterium rhizogenes. Phytochemistry, 30 3277-3280. 

Robins, R. J., Parr, A. J., Payne, J., Walton, N. J. and Rhodes, M. J. C. 1990. Factors regulating tropane alkaloid production in a transformed root culture of a Datura Candida x Datura aurea hybrid. Planta, 181 414-422. 

Villegas, M., Leon, R. and Brodelius P. E. 1999. Effects of alginate and immobilization by entrapment in alginate on benzophenanthridine alkaloid production in cell suspension cultures of Eschscholtzia californica. Biotechnology Letters, 21(1) 49-55. 

Nef, C., Rio, B. and Chrestin, H. 1991. Induction of catharanthine synthesis and stimulation of major indole alkaloid production by Catharanthus roseus cells under non-growth-altering treatment with Pythium vexans extracts. Plant Cell Reports, 10 26-29. 

Hashimoto, T., Yukimune, Y. and Yamada, Y. 1986. Tropane alkaloid production of Hyoscyamus root cultures. Journal of Plant Physiology, 124 61-75. 

A. Wilkinson. Stability of alkaloid production in flue—cured tobacco. Comp Sci 1991 31(5) 1121-1124. 

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