Unravelling the biosynthesis and mode of action of specialized metabolites

Abstract

Since decades, the excessive use of antibiotics has led to an enormous spread of multi-drug resistant (MDR) bacteria. Therefore, researchers show renewed interests in natural antibiotics, like secondary metabolites, as potential source of new drugs. Secondary metabolites are synthesized by large enzymatic assembly lines. Past years, researchers wanted to create new hybrid lines, thereby trying to expand the natural antibiotics pool. However, to date, attempts to assemble new pathways have not been a great success. Many times, production of new metabolites was completely abolished. An important explanation for these problems is the lack of knowledge about protein interactions, necessary to connect the different domains and modules. This PhD project aims to create new tools to combat the spread and danger of MDR bacteria. This will be realized by identifying protein interactions present in secondary metabolite assembly lines, followed by the development of an innovative domain assembly approach based on the acquired insights on protein interactions. The ultimate goal of this research is the development of new antibacterial molecules, ready for (pre)clinical testing.status: publishe