Plant cell cultures, synthesis

Kolewe ME, Gaurav V, Roberts SC. (2008) Pharmaceutically active natural product synthesis and snpply via plant cell culture technology. Mol Pharm 5 243-256. 

As de novo synthesis has been proven unsuccessful in most cases, biotransformation of added precursors has been studied extensively. There is evidence that plant cell cultures retain an ability to transform specifically exogenous substrates administered to the cultured cells. Therefore, plant cell cultures are considered to be useful for transforming cheap and plentiful substances into rare and expensive compounds by using the cell culture as a bioreactor. For instance, cofactor dependent specific conversions of terpenoids in suspension cultures of aromatic plants often proceed with high yields and negligible amounts of byproducts. In Fig. (1), three examples of biotransformations of terpenes by plant cell cultures are shown (after [6]). 

Kutney JP (1990) Biosynthesis and synthesis of indole and bisindole alkaloids in plant cell cultures a personal overview. Nat Prod Rep 7, 85-103. 

Carbon dioxide is, of course, fundamentally important to plants because of photosynthesis. Most plant cell cultures are heterotrophic, non-photosynthetic and use a chemical energy source. It is reasonable to suspect, however, that some of the control mechanisms for the photosynthetic dark reactions would be regulated by C02 concentration. This could affect both cell growth and, indirectly, production of useful compounds. More concretely, C02 is known to promote synthesis of ethylene [38] on the other hand, C02 concentrations of 5-10% inhibit many ethylene effects [53]. 

Although the main objective of present publications is the synthesis of pure flavour chemicals by plant cells there is a number of experiments with plant cell cultures for the manufacturing of complex flavour extracts. In these cases it is intended to produce flavour extracts using cell cultures of taste-delivering plants similar to the extracts rendered by extraction from the natural mother plant. 

Economically more meaningful would be the ab initio-synthesis of complex natural compounds by plant cells from CO2 and light. For this purpose the chlorophyll containing green parts (chloroplasts) of the plants would be needed which are able to effect photosynthesis. Only laboratory results are available in this area. More advanced results about flavour generation in plant cell cultures are available for ... 

Fowler, M. W., Cresswell, R. C., Stafford, A. M. An economic and technical assessment of the use of plant cell cultures for natural product synthesis on an industrial scale. In Bioactive Compounds from Plants (Chadwick, D. J., Marsh, J., Eds). John Wiley Sons Chichester, 1990, pp. 228-238. 

After their discovery, the Vinca alkaloids became the first natural anticancer agents to be clinically used, and they are still an indispensable part of most curative regimens used in cancer chemotherapy nowadays. On the other hand, the plant producing these alkaloids, C. roseus, has become one of the most extensively studied medicinal plants. The levels of vincristine and vinblastine in the plant revealed to be extremely low and, for pharmaceutical production, approximately half a ton of dry leaves is needed to obtain 1 g of vinblastine [4]. This feet stimulated intense investigation in alternative methods for the production of vinblastine and vincristine, namely chemical synthesis and plant cell cultures. However, chemical synthesis showed not to be viable due to the high number of transformations involved, and the anticancer alkaloids were never detected in cell cultures, which express alkaloid metabolism very poorly [5, 6]. The biosynthetic pathway of terpenoid indole alkaloids in C. roseus has also been intensively studied with the objective of developing a manipulation strategy to improve the levels of the anticancer alkaloids in the leaves of the plant [5, 7-10]. 

I. is used as a plant growth regulator. For synthesis, see Ul.. The biosynthetic precursor of I. is considered to be L- tryptophan Biosynthetic studies have been performed with Agrobacterium tumefaciens transformed plant cell cultures. For detection, see Lit.. lU. J. Heterocycl. Chem. 29,953-958 (1992) J. Am. Chem. Soc. 116, 3127 (1994). Aust. J. Plant Physiol. 20. 527-539 (1993). Plant Growth Regul. 10, 313-327 (1991). Pharis. Rood Stewart (eds.). Plant Growth Subst., p. 441 -449, Berlin Springer 1990. 

C21H24N2O2, Mr 336.43, mp. 196 C (as hydrochloride), (aJi) +310° (CHjOH). T. is a member of the Aspido-sperma alkaloids and occurs in numerous genera and species of the Apocynaceae. For biosynthesis, see monoterpenoid indole alkaloids. T. is a precursor of vindoline a building block of the dimeric alkaloids " vinblastine and " vincristine. T. is also formed in plant cell cultures but under these conditions cannot be completely transformed to vindoline. The biosynthesis of the dimeric alkaloids is not possible in cell cultures. For synthesis, see Lit.. ... 

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