Cellular aggregation is a key parameter associated with long term variability in paclitaxel accumulation in Taxus...

Plant cell cultures provide a renewable source for synthesis and supply of commercially valuable plant-derived products, particularly for secondary metabolites. However, instability in product yields over multiple passages has hampered the efficient and sustainable use of this technology. Paclitaxel accumulation in Taxus cell suspension culture was quantified over multiple passages and correlated to mean aggregate size, extracellular sugar level, ploidy, and cell cycle distribution. Paclitaxel levels varied approximately 6.9-fold over the six-month timeframe investigated. Of all of the parameters examined, only mean aggregate size correlated with paclitaxel accumulation, where a significant negative correlation (r = - 0.75, p < 0.01) was observed. These results demonstrate the relevance of measuring, and potentially controlling, aggregate size during long term culture passages, particularly for plant suspensions where industrially relevant secondary metabolites are not pigmented to enable rapid culture selection.