Alkaloid production, plant biotechnology

Verpoorte R, van der Heiden R and Memelink J (1998) Plant biotechnology and the production of alkaloids prospects of metabolic engineering. The Alkaloids, Chemistry and Pharmacology (ed Cordell GA) Vol 50. Academic, San Diego, pp 453-508. 

In a discussion on downstream processing of alkaloids produced by plant cell biotechnology, two quite different cases can be distinguished, namely, product stored in the biomass and product excreted by the biomass. The first case is comparable with the classic production of alkaloids from plant materitd, although specific problems could arise from the character of the cellular biomass. In the second case a variety of advanced separation techniques could be used. A typical example from plant cell biotechnology is the forced release of alkaloids. In the following sections product recovery from biomass as well as product release and product recovery from spent media are discussed. 

In Table XIV through XVIII the occurrence of alkaloids in various types of cell and tissue cultures of Atropa, Datura, Duboisia, Hyoscyamus, and various other species in the family Solanaceae is summarized. From these data it is clear that the production of tropane alkaloids in cell suspension cultures is rather low. Only in root cultures has production similar to, or even higher than, the original plant been obtained. For this reason an extensive discussion on efforts to improve production in cell suspension cultures is not useful instead, we briefly deal with the application of plant biotechnology for the improvement of the tropane alkaloid-producing plants. Finally, we discuss the bioconversion of added precursors. 

The development of plant cell biotechnological production of berberine by Coptis cells seems so far to be quite successful. Yields have been improved from a meager 2.4 mg of berberine hydrochloride isolated from 3.8 g of callus (0.06% of DW) (512) to 7 g/liter (10% of DW) (59), that is, an increase of more than 150 times the alkaloid levels in the cells. Several aspects can be pointed out that have contributed to this. First, all callus cultures induced do produce the desired product. Further, because of the yellow color of the alkaloid subsequent selection is easy to perform visually. Finally, the alkaloid production of cell cultures proved to be stable after repetitive selection. 

Modern biotechnological methods of producing potentially useful alkaloids, particularly plant cell culturing, is an area of fundamental importance and has been receiving a lot of attention. An analysis of the state of the art and where it is headed is discussed here by a well-known group from The Netherlands in Plant Biotechnology for the Production of Alkeiloids Present Status and Prospects. ... 

Yamada, Y., Yun, D.J., and Hashimoto, T. 1994. Genetic engineering of medicinal plants for tropane alkaloid production. In Ryu, D.D.Y. and Furusaki, S. (eds.). Advances in Plant Biotechnology. Elsevier Science Publishers, Amsterdam, the Netherlands, pp. 83-93. 

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