Production of Paclitaxel and Baccatin III in a 20-L Airlift Bioreactor by a Cell Suspension of Taxus wallichiana

Abstract

A cell suspension culture of Taxus wallichiana (Himalayan Yew) was grown in shake flasks and a 20-L airlift bioreactor running for 28 days in a batch mode, and its capacity to accumulate paclitaxel and baccatin III was measured. When both culture types were in the highest productive state (from day 24 to day 28), there was a greater accumulation of paclitaxel and baccatin III in the bioreactor culture than in the shake flask culture (factor of 2.0 and 1.2, respectively). These increases in paclitaxel and baccatin III production cannot be related to the difference observed between the growth rates of both cultures, because when the bioreactor culture was at maximum productivity, its cell biomass, expressed in g L(-1) of dry weight, was similar to that obtained in the shake flask culture. It seems that these improvements were mainly due to adequate aeration and mixing of the culture in the bioreactor. The maximum yield observed for paclitaxel (20.84 mg x L(-1) day 24) and baccatin III (25.67 mg x L(-1) day 28) represents a productivity of 0.90 mg x L(-1) d(-1) and 0.93 mg x L(-1) x d(-1) respectively.

Taxane Production in Suspension Culture of Taxus × Media var. Hicksii Carried Out in Flasks and Bioreactor

“…During culturing, the excretion of both taxanes in cells grown in flasks and in the bioreactor exceeded on average 72% of the total compound content which is consistent with results obtained by Navia-Osorio et al (2002) and Pestchanker et al (1996) although Wickremesinhe & Arteca (1994) reported only a 10% release of paclitaxel in suspension culture of Taxus · media. It was earlier demonstrated that at low inoculum sizes of 1.5 and 2.0 g dry wt l )1 the extracellular paclitaxel concentration was relatively higher (Wang et al 1997) which is in accordance with our results.…”

“…On the other hand, the consumption of sucrose in flasks corresponded well to the cell growth profile, and was 90% exhausted by day 14 --at the onset of stationary growth phase. Navia-Osorio et al (2002) also reported the lack of the lag phase after inoculation in experiments conducted in 20-l bioreactor. Data recorded during cultivating cells in bioreactor might be contributed to higher cell damage by sharing as the medium stirring was set at 400 rpm.…”

Enhancement of Taxol production by applying amino acid complex along with chitosan in suspension culture of Taxus baccata L.

“…Therefore, tissue culture offers a practical alternative to Taxol production. Being capable of performing a precise control of the production conditions, applying production stimuli such as elicitors and the ease of extraction in short time, are the main advantages of this system [6][7]. The use of elicitors of plant defense mechanisms has been one of the most effective strategies for improving the productivity of Taxol and many other useful secondary metabolites in plant cell cultures [8].…”

Taxus globosa Schltdl. (Mexican yew) and Taxus baccata L. (European yew): intra and interspecies analysis of taxol content and biological activity according to different sources

“…In The Netherlands, van Rozendaal et al, (2000) reported the production of taxol and related taxanes in Taxus species, which include T. globosa as a species with highest content, not only of taxol, but also its precursors, which easily can be chemically bioconverted into cultures of T. baccata L. (Bentebibel et al, 2005), Taxus canadensis (Nikolakakis et al, 2000), in the hybrid Taxus media (Taxus baccata x Taxus cuspidata) (Bonfill et al, 2003) and Taxus wallichiana Zucc., (Navia-Osorio et al, 2002;van Rozendaal et al, 2000).…”