Alkaloids from biotechnology

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. 

Nitrogen content in different soils after 1 year from sample preparations. Diagram of the links between areas connected to alkaloidal applications produced by biotechnology. 

From a biotechnological point of view, the impact of molecular genetics lies mainly in the detailed analysis of the biosynthetic pathway and in the option to create new alkaloids with higher pharmacological value, especially those showing a new or more specific mode of action. This is especially interesting... 

As these alkaloids are not only used in chemistry as chiral auxiliaries, starting materials, and catalysts, but also in medicine, so technical syntheses have been developed and all of these compounds are commercially available. The standard materials ( )-(l/ ,2,S )-ephedrine [(-)-3) and ( —)-(lff,25,)-norephedrine [(-)- ] are produced in a technical process on multikilogram scale by reductive amination (with methylamine or ammonia, respectively) of (—)-(f )-l -hydroxy- Tphenyl-2-acetone with a platinum catalyst1. The ketone is in turn obtained by a biotechnological procedure from cultures of selected yeast strains (Saccharomyces sp.)2. 

Shikonin is not an alkaloid, but because it is the first product from a plant cell biotechnological production, it is included in the table to enable comparison with the alkaloids. 

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 bisbenzylisoquinoline alkaloid tubocurarine would be an obvious goal for biotechnological production. However, to our knowledge no reports on cell cultures of Chondodendron tomentosum, the plant from... 

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. 

Of the various pharmaceuticals derived from plants, the Cinchona alkaloids are probably, by volume the largest market, with an estimated production of 300-500 metric tons a year of pure quinine (32) and quinidine (33). These alkaloids are extracted from the bark of Cinchona trees, which require about 10 years to mature before harvesting. Furthermore most of the plantations are in areas not easily accessible, often threatened by infections with Phytophthora cinnamomi. This leads to many uncertainties in planning of the production, and as a result alternative sources for the alkaloids are of interest. Various synthetic aproaches have been used (552) but are not of industrial interest. Therefore, interest in biotechnological approaches is large. Patents related to the production of quinoline alkaloids by means of plant cell cultures are summarized in Table XXVIII. 

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. ... 

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