Engineering of Plant Metabolism for Drug and Food

Directing metabolic fluxes in plants for the production of nutraceuticals or fine chemicals (e.g. drug precursors) is becoming increasingly attractive and feasible. We review first recent accomplishments of plant metabolic engineering. Both experimental evidence and theoretical predictions point out that (i) metabolic flux increases require manipulation of most of the enzymes in a biosynthetic pathway, (ii) modulating all enzymes in a pathway avoids extremes in metabolite concentration in the pathway and causes little disturbance in connected pathways. On these basis we conclude that the most general and effective way forward for increasing the production of plant metabolites is to manipulate factors which specifically and co-ordinately regulate the expression most of the genes coding for the enzymes of a biosynthetic pathway. We therefore discuss the methods to acquire knowledge on the regulatory circuitry of transcription of genes involved in metabolic pathways and the strategies to manipulate it. Providing precursors to the pathway and removing the product, which can be accomplished by creating metabolic shortcuts and engineering energy dependent pumps specific for product removal, are part of the strategy. Keywords: metabolic engineering, metabolic pathway, transcription factor, flux, feedback regulation, microarray, genomewide location