Development of a hazel cell culture-based paclitaxel and baccatin III production process on a benchtop scale

The growing demand for the antitumorous agent paclitaxel and the difficulty in increasing its productionby genetic engineering has prompted a search for new sources of taxanes. It has been reported that taxane scan be extracted from the angiosperm Corylus avellana L. Our aim was to improve taxane productionby scaling up the process from mL-level to benchtop bioreactors, optimizing culture conditions and comparing the effect of two elicitors, 1 mu M coronatine (Cor) and 100 mu M methyl jasmonate (MeJA). Orbitally shaken flask cultures achieved a maximum fresh cell weight of 11.54 g(DCW)/L under control conditions, and MeJA- and Cor-treatment produced a statistically significant reduction in growth to 4.28 g(DCW)/L and 5.69 g(DCW)/L, while increasing the taxane content 3- and 27-fold, respectively. The enhancing effect of these elicitors on taxane production, despite affecting growth, was confirmed in orbitally shaken TubeSpin (R) Bioreactors 50, where the highest taxane content (8583.3 mu g/L) was obtained when 1 mu M Cor was used and elicitation took place at a packed cell volume of 50%. Two benchtop stirred bioreactors, BIOSTAT (R) B plus and UniVessel (R) SU, were compared, the latter providing a higher biomass of C. avellana cell suspension cultures. Transferring the established optimum culture conditions for taxane production to the UniVessel (R) SU resulted in a total taxane content of 6246.1 mu g/L, a 10-fold increase compared with shake flask experiments. (C) 2015 Elsevier B.V. All rights reserved.