Ditte Hededam Welner
Senior Researcher & Group Leader
Novo Nordisk Foundation Center for Biosustainability
Building 220 Room 504F
2800 Kgs. Lyngby
High-throughput methods Protein Chemistry Enzyme Engineering Structural Biology
Enzyme Engineering and Structural Biology We develop enzyme biocatalysts for the industrial production of natural products used as e.g. aromas, fragrances, dyes, and pharmaceuticals. The existing industrial pipelines have large environmental footprints due to their use of petroleum-derived, hazardous materials and their generation of toxic waste streams. Therefore, replacing the current chemical synthesis routes with bio-based processes including cell factories and chemo-enzymatic approaches will constitute a significant step towards a greener society. In nature, many natural products are glycosylated by an enzyme class termed secondary metabolism glycosyltransferases (GTs). Glycosylation alters the physico-chemical properties of the natural product, including solubility, stability and bioavailability. We aim at harnessing this glycosylation activity for industrial purposes by tailoring secondary metabolism GTs for specific pipelines. Thus, we are engaged in a systematic study of secondary metabolism GT structural and functional determinants, to provide the framework for efficient secondary metabolism GT discovery and engineering. We combine high-throughput enzyme discovery and evolution with structure-based rational engineering to elucidate the structural determinants of key enzymatic properties such as Substrate specificityEnzymatic efficiencyThermostability and pH tolerance Our core methods are X-ray crystallography, enzymology, and other classical protein chemistry techniques for biophysical characterization.