Molecular genetics of natural producers
Research focus of the Stegmann lab
Our research is focused on the discovery and investigation of interesting secondary metabolites. By employing “Genome Mining” we identify biosynthetic gene clusters of compounds with particular bioactive properties and unusual chemical features. Using genetics, biochemistry and chemical methods we elucidate the stepwise biosynthesis of the molecules. This enables us to engineer the respective pathways in order to optimize the production and to generate novel derivatives with better properties (e.g. by mutasynthesis experiments).
Another strong focus of our research is on the interconnection of the primary and secondary metabolism in the producer strains. The metabolic pathways of the primary metabolism often supply the precursors of the antibiotics. There is an early common part, which then branches to the synthesis of a primary metabolite on the one hand and to a secondary metabolite on the other. We redirect the flux into the secondary metabolite branch in order to optimize the production.
Apart from the research on the biosynthesis of secondary metabolites we are also investigating the self-resistance mechanisms of the producer strains. To protect themselves from their own product, antibiotic producers developed self-resistance mechanisms. Inspection of different producer strains revealed that their resistance is not only based on a single determinant but on the synergistic action of different factors.
The Stegmann group applies these approaches mainly to bacteria of the genus Amycolatopsis, producers of clinical relevant antibiotics. We developed different methods to genetically manipulate the strains.
Our projects are funded by
- Genetic manipulation of Amycolatopsis strains
- Genome mining
- Synthetic biology
- Metabolic engineering
- Self-resistance mechanisms of producer strains