Metabolic engineering of Saccharomyces cerevisiae for the production of aromatic compounds

Over the past century, the world population has increased fourfold. This increase in human population is accompanied by an increased demand in food, water, energy and consumer goods. The resulting intensification of agriculture, deforestation, emission of green-house gasses and high utilization of natural compounds such as coal, minerals, metals and fossil-fuels have resulted in global warming and a depletion of Earth’s natural reserves. The application of biotechnology can aid in the transition to a more sustainable, circular and bio-based economy. For example, by offering novel production processes for a range of different compounds, such as therapeutics, beverages, food, chemicals and fuels from renewable sources. For instance, Baker’s yeast is known for its natural ability to produce CO2 and ethanol from sugars, characteristics that were historically exploited for the production of alcoholic beverages and bread. Today, bio-ethanol as transportation fuel made by yeasts also provides a more sustainable alternative to gasoline. Additionally, due to the enormous increase in knowledge and the establishment of genome editing tools and sequencing possibilities, biotechnology can now apply genetically engineered microbes to produce an ever-increasing range of products, both native or heterologous, to the microorganism. For example, micro-organisms have been engineered to produce complex molecules such as human insulin, the flavoring compound vanillin and the antimalarial drug artemisinin. Insulin, which is essential for treatment of diabetes, was conventionally produced by extraction from pig pancreas, while artemisinin and vanillin were extracted from plants, or in case of vanillin, also synthesized chemically. However, microbial production of such industrially valuable compounds, from simple substrates such as glucose or second-generation feedstocks, offers a more reliable and sustainable production method compared to these classical methods. In this thesis special emphasis is given to the Baker’s yeast Saccharomyces cerevisiae and its application in the production of aromatic compounds. There is an increasing interest in the microbial production of aromatic molecules, such as in the flavor and fragrance industry. The economic potential of this field is partly due to European legislation, that allows the production and sale of microbially produced molecules, as long as the final product is devoid of genetically modified organisms (GMOs). S. cerevisiae is able to natively synthesize several aromatic compounds, although their production is limited by tight regulation of the involved pathways. Many other industrially attractive aromatic compounds find their origin in plants. In order to establish yeast-based production of these aromatic molecules, it is necessary to both introduce plant genes, and modify, the metabolism of S. cerevisiae to obtain fast and efficient production...