We report here the effect of lauryl alcohol (LA), an effective organic solvent for in situ extraction for production of paclitaxel, on the production of taxanes (10-deacetyl baccatin III, baccatin III and cephalomannine) in a suspension callus culture of Taxus cuspidata. The culture conditions for enhancing production of the taxanes by avoiding feed-back inhibition of paclitaxel were examined. Increased callus growth and production amounts of the taxanes except cephalomannine were obtained in the LA-medium culture systems compared to the control culture where LA was not added. This result suggested that LA influenced the cellular and/or enzymatic activities involved in the biosynthetic pathway of paclitaxel.
A fatty alcohol, lauryl alcohol (LA), has been found to be an effective organic solvent for in situ extraction and production of paclitaxel in a suspension plant cell culture.The culture procedure and/or conditions for enhancing paclitaxel productivity by avoiding feed-back inhibition have been studied. 5-aminolevulinic acid (ALA), which promotes plant growth, was used for this purpose in the LA-medium two phase culture systems and its effect on the paclitaxel productivity in the culture was examined. Similar callus growth and greater paclitaxel production were observed in the two phase culture systems including ALA compared to the control culture with no treatment. Enhanced paclitaxel production was recorded due to the decreased paclitaxel concentration in the medium avoiding its feed-back inhibition and the increased cellular activity by ALA. Paclitaxel productivity increased by a factor of 3 compared to the control.
We report here the development of a new bioreactor (bioreactor with foam separation, BFS) for efficient production and recovery of paclitaxel that circumvents paclitaxel's inhibitory effects on growth through a feedback mechanism. The BFS captures paclitaxel through its hydrophobic interaction with the foam generated by aerated culture medium. The BFS comprises co‐axial 0.65 dm3 outer (150 mm height and 75 mm diameter) and 0.15 dm3 inner vessels (90 mm height and 50 mm diameter) equipped with a ball‐type sparger (5–10 µm pore size, 10 mm diameter) and a wire‐framed draft tube covered by a water‐permeable cellulose bag (150 × 40 mm, 100 µm maximum pore size). The BFS was tested by adding paclitaxel alone to the medium of 0.12 dm3 in the inner vessel and collecting it in the foam that overflowed into the outer vessel. Paclitaxel was separated with first‐order kinetics and was optimally recovered using an aeration rate of 0.05 dm3 min−1 (0.21 vvm). Next, a Taxus cuspidata callus was cultured using the optimal aeration rate. A conventional shaking culture (110 rpm) served as the control using a 0.2 dm3 Erlenmeyer flask (0.12 dm3 medium). Paclitaxel was maintained at less than 0.02 g m−3 in the inner vessel of the BFS. Consequently, there was no feedback inhibition, and the paclitaxel production increased by a factor of five in the BFS compared with the control culture where there was feedback inhibition by the high concentration of paclitaxel. © 2013 Curtin University of Technology and John Wiley & Sons, Ltd.
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