Biotechnological production of taxanes: a molecular approach

Abstract

Plant cell cultures constitute a promise for the production of a high number of phytochemicals, although the majority of bioprocesses that have been developed so far have not resulted commercially successful. An overview indicates that most of the research carried out until now is of the empirical type. For this reason, there is a need for a rational approach to the molecular and cellular basis of metabolic pathways and their regulation in order to stimulate future advances. The empirical investigations are based on the optimization of the culture system, exclusively considering input factors such as the selection of cellular lines, type and parameters of culture, bioreactor design and elicitor addition, and output factors such as cellular growth, the uptake system of nutrients, production and yield. In a rational approach towards the elucidation of taxol and related taxane production, our group has studied the relationship between the taxane profile and production and the expression of genes codifying for enzymes that participate in early, intermediate and late steps of their biosynthesis in elicited Taxus spp cell cultures. Our results show that elicitors induce a dramatic reprogramming of gene expression in Taxus cell cultures, which likely accounts for the enhanced production of taxol and related taxanes and we have also determined some genes that control the main flux limiting steps. The application of metabolic engineering techniques for the production of taxol and taxanes of interest is also discussed.