D 6 - Michael Bölker

Production of secondary metabolites in response to complex and changing environments








Prof. Dr. Michael Bölker

Philipps-Universität Marburg, Faculty of Biology

Karl-von-Frisch-Straße 8, 35043 Marburg

+49 - 6421 - 2821536




Research summary:

Many microorganisms react to changes in the environment and stress with the production of secondary metabolites. These substances serve for many different purposes and protect against damage, allow the acquisition of nutrients or help to compete with other microorganisms. During the last funding period we discovered two novel gene clusters for secondary metabolites in the phytopathogenic fungus Ustilago maydis.

(i) We have identified a gene cluster that contains all genes required for the biosynthesis of the unsaturated dicarboxylic acid itaconate. Interestingly, U. maydis produces itaconate not via decarboxylation of cis-aconitate as has been described in other  organisms but by trans-aconitate decarboxylation. Both itaconate and trans-aconitate act as enzyme inhibitors and thus are toxic. We will focus on the metabolic regulation and biological function of these two unusual metabolites. We detected that U. maydis contains a gene cluster that contains genes to enable the usage of trans-aconitate as nutrient. The catalytic mechanism of the U. maydis enzymes involved in itaconate and trans-aconitate metabolism is unknown und therefore we will use X-ray crystallography to determine their secondary and tertiary structure. In addition, we will study how U. maydis evades the toxic effects of both itaconate and trans-aconitate. Transcription of genes involved in trans-aconitate metabolism is stroingly induced by trans-aconitate. We will study, how U. maydis senses transaconitate and how this metabolite is taken up by the cells.

(ii) During its pathogenic development U. maydis produces dark spores. Recently, a polyketide synthase and a laccase were described, that are responsible for spore melanization. By genome analysis we could identify an additional gene cluster that causes melanization independent of spore formation. This cluster encodes three polyketide synthases and contains further genes characteristic for secondary metabolism. Forced expression of a pathway-specific transcription factor resulted in the production of a dark pigment in axenic culture. Preliminary structural analysis revealed that the dark pigment consists of polymerized tetrahydroxynaphthalene (THN) monomers. This finding was surprising because most fungi produce either dihydroxynaphthalene (DHN) or tyrosine derived (DOPA)-melanin. During the next period we will therefore further study the biosynthetic pathway and the molecular structure of this unusual melanin. To get a clue to the biological function of THN-melanin we will determine how activation of the gene cluster occurs and under which environmental conditions the second melanin gene cluster is expressed.