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Function and production of secondary metabolites

Final Report Summary - PROSECMET (Function and production of secondary metabolites)

The goal of the ERC starting grant PROSECMET was to address the production of natural products from insect-pathogenic bacteria of the genera Xenorhabdus and Photorhabdus. Such natural products (NPs) could have potential as antibiotics or other drugs and the goal was to develop strategies to get to these compounds faster.
This was achieved initially mainly by the development of several molecular microbiology methods that allowed a "on-demand" production of the natural products based on a promoter exchange of the respective biosynthesis gene clusters. Later, this method was coupled to promoter exchange in hfq deletion mutants that hardly produced any NPs anymore and thus allowed a much simpler isolation of these NPs. These finding also connected the biology of small regulatory RNAs with classical NP research that might result in the creation of a new interdisciplinary research area.
During PROSECMET methods were developed that allow the simple modification of non-ribosomal peptide synthetases (NRPS) with high efficiency. The newly identified molecular "Lego"-like assembly of these enzymes allows the production of completely new NPs that might in the future lead to the development of novel peptide based drugs.