Deciphering and Pushing Whole-Cell Catalysis
Modern society relies intensely on commodity chemicals, whose global market accounts for more than €3.6 trillion yearly. Currently, 95% of the chemical production is covered by synthetic chemical processes, which often employ rare-metal catalysts, in combination with energy-intensive procedures and polluting solvents, thus being responsible for significant amounts of greenhouse gas direct emissions. Most of the chemicals that are needed for our everyday life can realistically be produced from biological systems, such as whole microorganisms like Baker´s yeast, which are more sustainable, produce less waste and are capable of catalyzing reactions yielding high-quality products. Microorganisms possess many hidden properties, which are difficult to discover and exploit when no tools are available to look inside the cells quickly and directly.
In this PhD thesis, non-invasive analytical tools, i.e. Nuclear Magnetic Resonance (NMR) and sensitivity-enhanced NMR, were developed and optimized to have a direct insight into intracellular chemistry changes which can lead to the discovery of new valuable molecules produced by cells subjected to different feeding sourced and stressors. By providing the cells with a mixture of carbon sources and by employing these optimized analytical tools, compounds relevant in the drug-, fine- and chemical industry were produced by the sole use of commercial yeast. Moreover, the optimized NMR tools were employed to track the alteration of metabolism in cancer cells and to distinguish the usage of specific pathways in different type of microorganisms, to gain knowledge on how diverse species have evolved to form different molecules.
Principal Supervisor:
Associate Professor Sebastian Meier, DTU Chemistry
Co-supervisors:
Associate Professor Pernille Rose Jensen, DTU Health Tech
Professor Robert Madsen, DTU Chemistry
Examiners:
Associate Professor Charlotte Gotfredsen, DTU Chemistry
Professor Finn Aachmann, Norwegian University of Science and Technology, Trondheim
Principal Scientist, Flemming Hofmann Larsen, Leo Pharma
Chairperson:
Associate Professor René Wugt Larsen, DTU Chemistry