Functional genomic approaches to study and engineer secondary metabolism in plant cell cultures

Abstract

Plants produce a wide range of secondary compounds, also referred to as natural products, which may have important functions in the plants adaptation to specific ecological niches or its responses to biotic and abiotic stresses. Some of these secondary metabolites turn out to be beneficial for humans as pharmaceuticals. Because of their unique and often complex chemical structures, synthesis of these natural compounds is frequently unfeasible or not economically justified. Therefore, many secondary metabolites are still extracted from whole plants. However, they are often produced only in certain tissues, at specific developmental stages or they are present in low concentrations. The possibility of growing medicinal plants, either as a whole, or as a specific tissue or even as plant cells in so-called tissue culture is intensively being investigated. Nevertheless, only few examples of commercial exploitation of plant cell cultures to produce a natural product exist, mainly due to the low yields and the instability of production rates commonly encountered in cell culture systems. Emerging tools such as metabolic engineering have added little to the production problem, since insight into the molecular mechanisms driving plant secondary metabolism at present is fairly limited. Knowledge of the genetics of biosynthetic pathways and their regulation is thus of crucial importance to bypass the low yield of various secondary metabolites in plant cells. To facilitate gene discovery in plant secondary metabolism, in our department a comprehensive profiling approach has been developed that is based on functional genomics. This approach integrates cDNA-AFLP-based transcript profiling and targeted metabolic profiling. As this method requires no prior genetic knowledge or sequence databanks, it is applicable to any plant species to unravel the biosynthesis of any metabolite of interest. This knowledge will then allow for metabolic engineering, as well as pave the way for so-called ‘combinatorial biochemistry’, with which novel metabolites could be produced in plants