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

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.

Microbial paclitaxel: advances and perspectives

“…Cell culture systems were successfully developed for large-scale paclitaxel production even though complex and specialized techniques, with long incubation times, are required. [8][9][10][11][12] In spite of the remarkable progress in the different production alternatives during the past two decades, paclitaxel remains an expensive compound. Consequently, more economic supply is still required so that paclitaxel can be accessible to more people in the world.…”

In Vitro Plant Cultures as Biofactories

“…Chapter 3 covers plant secondary metabolism and the biological activities secondary metabolites display as their participation in defence against herbivores (insects, molluscs, vertebrates), and microorganisms (virus, bacteria, fungi), and their metabolic and ecological functions (attracting pollinators, animals that spread seeds, UV protection) (Wink 1988 ;Wink et al 2005 ).…”

Plant Cell-Based Bioprocessing

“…For example, a pharmaceutical isolator is an integral part of the 50 L LCMB Bioreactor, a spray bioreactor of plastic film (Fig. 8.4k), which was introduced by Wink et al (2005) for the production of podophyllotoxin. To allow hairy root attachment to the immobilization matrix, ebb-and-flow mode operation was included.…”