Integrated transcript and metabolite profiling of the medicinal plant Catharanthus roseus

Plant-derived secondary metabolites still constitute important resources for currently prescribed drugs and for the discovery of active principles which are effective in new indication areas. The medicinal plant Catharanthus roseus (L.) G. Don has been extensively investigated during the last decades in order to utilize cell culture systems for the biotechnological production of important anticancer compounds e.g. vinblastine and vincristine. However, rational engineering of complicated metabolic networks such as the pathways leading to terpenoid indole alkaloids (TIAs) has been greatly impeded by our poor understanding of the regulation and structural organization underlying the biosynthesis. We have applied a comprehensive profiling approach based on functional genomics, which is independent of prior sequence knowledge, to monitor jasmonate-induced changes on the transcript and metabolite profiles of cell cultures. The behaviour of most of the currently known genes and metabolites involved in TIA biosynthesis plus hundreds of unknown elements could be observed in a single experiment. The integration of the expression profiles of 417 gene tags and the accumulation profiles of 178 metabolite peaks through correlation network analysis resulted in novel gene-to-metabolite networks revealing that the different branches of TIA biosynthesis as well as various other metabolic pathways are subject to differing hormonal regulation. These networks served also to identify a select number of genes and metabolites likely to be involved in the biosynthesis of TIAs. This study sets the base for a better understanding of periwinkle secondary metabolism and increases the practical potential of metabolic engineering of this important medicinal plant.