Bacteria are highly complex and diverse organisms that have adapted to survive in ecological niches ranging from the most extreme to the most heterogeneous environments. Actinobacteria, with their... Show moreBacteria are highly complex and diverse organisms that have adapted to survive in ecological niches ranging from the most extreme to the most heterogeneous environments. Actinobacteria, with their beautiful morphologies and complex multicellular life cycle, are a striking example. These filamentous bacteria produce many enzymes and natural products, including two-thirds of all known antibiotics, which makes them highly relevant for medical, biotechnological and industrial applications. In Streptomyces, complex and intertwining regulatory networks, consisting of pathway-specific and global regulators, control development and antibiotic production in response to environmental stimuli and stresses. This thesis explores how the model organism Streptomyces coelicolor senses environmental signals, related to oxygen stress and the availability of aminosugars, and how the bacterium translates these into appropriate responses. Show less
Plants produce a variety of secondary metabolites. In Catharanthus roseus, several have pharmaceutical applications, including the monomeric alkaloids serpentine and ajmalicine, which are used as a... Show morePlants produce a variety of secondary metabolites. In Catharanthus roseus, several have pharmaceutical applications, including the monomeric alkaloids serpentine and ajmalicine, which are used as a tranquillizer and to reduce hypertension, respectively, and the dimeric alkaloids vincristine and vinblastine, which are potent antitumour drugs. Jasmonic acid (JA) is a key defense hormone, which controls the expression of several alkaloid biosynthesis genes in Catharanthus. The JA-responsive expression is controlled by the AP2-domain transcription factors ORCA2 and ORCA3. The results in this thesis demonstrate that JA-responsive ORCA expression is controlled by an up-stream positive regulator, whose activities are affected by a family of repressors. Understanding the regulation mechanism may help to generate a very valuable tool for engineering the production of valuable secondary metabolites. Show less
Saccharomyces cerevisiae is one of the few yeast species that can grow equally well without molecular oxygen (anaerobic) as with this compound present (aerobic). This property has made it one of... Show moreSaccharomyces cerevisiae is one of the few yeast species that can grow equally well without molecular oxygen (anaerobic) as with this compound present (aerobic). This property has made it one of the most abundantly used yeasts in industry, since anaerobic incubation plays a major part in alcohol and bread industry. With the experiments described in this thesis it has been shown that apart from metabolic changes, an adaptation of the cell wall and the plasma membrane is very important for anaerobic growth. There seems to be a connection between this adaptation and the import of sterols, which are essential when no molecular oxygen is present. The importance of these adaptations becomes clear when the genomes of the facultative anaerobic Saccharomyces cerevisiae and the obligatory aerobic Kluyveromyces lactis are compared. K. lactis does not have any genes that encode for a sterol import system.The adaptation of the cell wall and the plasma membrane to anaerobic conditions is extensive and regulated in a complex way, as is apparent from the transcriptome data. Our experiments show that Snf7 is, at least in part, responsible for these changes. Show less
