Microorganisms are extensively used for diverse applications, ranging from food production to the synthesis of pharmaceuticals. Despite the fact that the bacterium Bacillus subtilis is a well-known and valuable "cell factory", bottlenecks have been described that limit the application possibilities (i.e. the biotechnological potential) of this bacterium. An attractive alternative expression host is ''miniBacillus PG10'', which was created by removing 36% of (redundant) genetic material from B. subtilis. In this thesis, we investigated the biotechnological potential of miniBacillus PG10 and explored possibilities for further optimization of this minimal cell factory. First, we developed a new production system for antimicrobial peptides and compared this system between different strains of B. subtilis. Our work shows that PG10 is a convenient and effective microbial cell factory, which has a number of advantages compared to other B. subtilis strains. We then further optimized PG10 by studying a defect in cell division that arose during the genome reduction process. In addition to finding a solution for this defect, we revealed new targets for further minimization of the genome of PG10. Another important part of this thesis was to analyze the organization of lipids and certain proteins in the membrane of PG10 and its parent strain. We also tested whether certain domains in the membrane can be used to improve biotechnological processes in a bacterial cell factory. This provided new insights into these membrane domains and how they can be exploited to increase the biotechnological potential of B. subtilis.
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2021|