Mankind has used microbes and their metabolisms for centuries. In contrast, the fine-tuning of the metabolic network through rationally designed gene constructs is a relatively new concept. While the use of genetically modified organisms has already been successfully implemented for the production of commodity chemicals, the reconstitution of pathways to bioactive natural products is still facing a number of challenges. Our group is engaged in the engineering of new platform organisms, including strains of Saccharomyces cerevisiae and Myxococcus xanthus, as well as in the development of genetic tools, which facilitate the refactoring of complex biosynthetic pathways.