DFG Priority Programme 1152
"Evolution of Metabolic Diversity"

The DFG Priority Programme SPP 1152 "Evolution of Metabolic Diversity" (EvoMet) was established to initiate a collaboration between plant scientists, microbiologists and chemists with the aim to investigate evolution and diversity of secondary metabolite formation.

Plant and microbial secondary metabolites form an immense reservoir of natural chemical diversity. The structures of more than 200,000 secondary metabolites have been elucidated to date. In contrast to primary metabolism, which is essential to the growth and development of an organism, secondary metabolism is not essential to these processes. Secondary metabolites are, however, required for the interaction of an organism with its environment. Fascinating examples of this exist in the area of defence against pathogens or competitors. The dynamic exchange between competing organisms further reflects the functional variety found in secondary metabolism. The natural plasticity of secondary metabolism underlies the ease with which microorganisms develop resistance to antibiotics and with which parasites and insects resist long-term chemical control. The manifold survival strategies of organisms have resulted in an arsenal of natural products with pharmacological, antibiotic, herbicidal, nematocidal and insecticidal activities. These compounds often have commercial relevance in direct use or serve as lead compounds for the development of new industrial products.

Each biosynthetic route of secondary metabolism derives from primary metabolism and involves complex and often highly specific reactions that lead to defined end products. In many cases, the first reaction that deviates from primary metabolism is pivotal to the formation of a new secondary biosynthetic pathway. This reaction gives rise to the first intermediate, which is further converted to a bioactive end product. Under natural selection the new pathway will be maintained. It is likely that the genes encoding enzymes and regulators of secondary metabolism were recruited from primary metabolism by gene duplication and subsequent diversification. In the course of evolution these duplicated genes acquired new functions and were optimised for their role in the new pathway.

Secondary metabolite-producing organisms ranging from bacteria to fungi and plants are being investigated in order to establish general principles of the evolution of the biosynthesis and regulation of secondary metabolite formation. We have joined together the previously separate efforts of natural product chemists, plant and microbial biochemists and molecular biologists to address the above questions with a multidisciplinary approach. The results obtained in this Priority Program have not only value in understanding basic natural principles, but also have a potential for practical application. A better understanding of the secondary metabolite biosynthetic enzymes can form the basis for directed enzyme evolution and combinatorial biochemistry, each useful in the synthesis of novel metabolites. A better understanding of the factors regulating secondary metabolism will be requisite to metabolic engineering of microorganism and plants with tailored natural product profiles.