Plant Genetic Resources: Characterization and Utilization

Research Article

Sustainable bioproduction of phytochemicals by plant in vitro cultures: anticancer agents

Michael Winka1 c1, A. Wilhelm Alfermanna2, Rochus Frankea1, Bernhard Wetterauera1, Melanie Distla1, Jörg Windhövela2, Oliver Krohna2, Elisabeth Fussa2, Hermann Gardena2, Abdolali Mohagheghzadeha3, Eckart Wildia4 and Peter Ripplingera4

a1 Institut für Pharmazie und Molekulare Biotechnologie, Universität Heidelberg, INF 364, 69120, Heidelberg, Germany

a2 Institut für Entwicklungs- und Molekularbiologie der Pflanzen, Universität Düsseldorf, Universitätsstr. 1, 40225, Düsseldorf, Germany

a3 Department of Pharmacognosy, Faculty of Pharmacy, Shiraz University of Medical Sciences and Health Services, Shiraz, Iran

a4 Rootec GmbH, 69123, Heidelberg, Germany

Abstract

Due to their complex structure with several chiral centres important anticancer agents are still extracted from plants and not synthesized chemically on a commercial scale. Sustainable bioproduction of the compounds of interest may be achieved by plant in vitro cultures. Undifferentiated callus and suspension cultures, which can be cultivated in large bioreactors easily, very often fail to accumulate the compounds of interest, whereas shoot and root cultures as well hairy roots normally produce the same compounds as in the appropriate organs. The production of anticancer compounds, such as the alkaloids vinblastine, vincristine, paclitaxel (Taxol®), camptothecin, or the lignan podophyllotoxin, by plant in vitro cultures is reviewed. Taxanes can be produced in bioreactors using cell suspensions of various Taxus species with good yields; presently paclitaxel is produced on a commercial scale by Phyton Biotech (Germany). Camptothecin has low yields in suspension cultures of Camptotheca acuminata or Nothapodytes foetida (0.0003–0.01%), but a good production (0.1–0.3% dry wt) in root and hairy root cultures of Ophiorrhiza pumila, O. mungos and C. acuminata. Podophyllotoxin can be produced in cell suspension and root as well as hairy root cultures of Podophyllum and various Linum species up to 130 mg/l (Linum album cell suspensions); its derivative 6-methoxypodophyllotoxin is accumulated in hairy roots of L. persicum up to about 500 mg/l. The in vitro production of dimeric indole alkaloids in Catharanthus roseus has failed so far both in undifferentiated and differentiated in vitro cultures. In cases where in vitro cultures show good yields, they can be employed in biotechnology for the sustainable production of valuable products.

(Received January 28 2004)

(Accepted May 02 2005)

Correspondence:

c1 *Corresponding author: E-mail: wink@uni-hd.de

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