Combinatorial biosynthesis has been successfully employed for e.g. carotenoid- and antibiotic polyketide-producing micro-organisms. It involves interchanging secondary metabolism genes between micro-organisms to create unnatural gene combinations or hybrid genes. Novel metabolites can be made due to the effect of new enzyme-metabolic pathway combinations or to the formation of proteins with new enzymatic properties.

Thus far, such an in vivo combinatorial biosynthesis approach has not been extended to higher plant systems, primarily for practical reasons and the lack of genetic tools for metabolic engineering of plant cells. The technology platform developed in our research group will offer the opportunity to browse into the entire metabolic repertoire of a plant and to assess the principle of combinatorial biosynthesis in plant cells. Within a multidisciplinary consortium, transcript and metabolite profiles, (transgenic) tissue culture collections and gene platforms from five different plants, all producing triterpene saponins, are being generated, characterized and exploited. The plants of particular interest are the model plant Medicago truncatula and the medicinal plants Glycyrrhiza glabra, Panax ginseng, Bupleurum falcatum and Maesa lanceolata, all producing saponins with either anti-inflammatory or anti-angiogenic activities. Notably, in all of these plant species, elicitation of saponin biosynthesis can be achieved by treatment with jasmonates. Combinatorial biosynthesis is pursued by piling up the newly identified potential saponin biosynthetic genes in transgenic Medicago and Maesa hairy roots, and in the yeast Saccharomyces cerevisiae, with the final aim of creating novel triterpene saponins with novel or superior biological activities.