Production of the anticancer compound camptothecin in root and hairy root cultures of Ophiorrhiza mungos L.

Abstract

Camptothecin (CPT), a modified monoterpene indole alkaloid, is a well-known antineoplastic agent. A comparison of 25 different transformed root culture lines of Ophiorrhiza mungos (hairy roots transformed by Agrobacterium rhizogenes), which produce CPT, showed a total CPT content of 890-3200 µg/g dry weight. Untransformed root cultures of O. mungos accumulated approx. 2000 µg CPT/g root tissue, or 2500 µg CPT of DW in total, respectively. Both transformed and untransformed root organ cultures of O. mungos showed high yields of CPT and therefore represent an interesting system for the feasible and sustainable bioproduction of CPT as raw material for the pharmaceutical industry. CPT production in other systems will be reviewed and compared. In the present study, comprehensive comparative kinetics of transformed and untransformed root organ cultures of O. mungos in relation to culture conditions, growth parameters, nutrient utilization, and CPT formations were determined. The absolute CPT content showed a positive correlation with growth; thus a constitutive CPT biosynthesis is assumed. CPT was released to the culture medium to a substantial degree. Media CPT content seemed to be actively regulated by the roots themselves, at least in the untransformed line, and exhibited a specific level for each line. The influence of the nitrogen source in relation to growth and CPT biosynthesis was investigated. Ammonium was preferred as a nitrogen source, but nitrate seemed to be beneficial and essential for pH value regulation and consequently for root growth and CPT biosynthesis.