Optimization of a broth conductivity controlling strategy directed by an online viable biomass sensor for enhancing Taxus cell growth rate and Taxol productivity

Abstract

Online process control is always an important and challenging technique for anti-cancer Taxol (paclitaxel) production by a plant cell suspension culture due to its slow growth rate, variability and intense sensitivity to environmental factors. In this work, we investigated the effects of a constant broth conductivity controlling strategy directed by an online viable biomass sensor on Taxol productivity of Taxus chinensis var. mairei in suspension cultivation. The viable cell capacitance was effectively used for detecting Taxus cell concentration online and for optimal feeding of the elicitor to stimulate Taxol production. An increase in conductivity has a negative effect on cell growth and elongation. With the optimal broth conductivity constantly controlled at 2.6 mS cm⁻¹ and methyl jasmonate at 6 μmol g⁻¹ cell, the Taxus cell growth rate and Taxol production reached their highest value at 0.87 g d⁻¹ and 76.2 mg L⁻¹ at 8 days after methyl jasmonate addition, and productivity reached its highest at 850 μg per g DCW per d, which was much higher than that under the higher conductivity conditions. Therefore, a substrate real-time feedback control strategy based on capacitance and conductivity must be an effective method for enhancing Taxol productivity and can be used for the scale up of a plant cell suspension culture.