Prof. Marco Fraaije is expert in the area of enzymology with a focus on discovery, engineering and applications of redox enzymes. He aims at unravelling the molecular basis by which cofactor-dependent redox enzymes perform catalysis. This includes investigations of: (1) how enzymes recognize, bind and activate their respective cofactors, and (2) how enzymes perform catalysis. The generated knowledge is used for mechanism- and structure-inspired enzyme redesign approaches.
Key findings are the elucidation on how oxygen-dependent enzymes (oxidases and monooxygenases) sequester dioxygen, tunnel dioxygen towards the right entry of the active site, and how it is used for catalyzing oxidations. Such detailed insight has led to the redesign of a dehydrogenase into an oxidase and the redesign of a monooxygenase into and oxidase.
The enzyme discovery and engineering efforts typically focus on enzymes that are capable of catalyzing industrially relevant reactions. An example of a recently discovered oxidase that has attracted attention of many academic and industrial research groups is 4-hydroxymethyl-furfural oxidase. Another class of enzymes for which Fraaije has uncovered structural and mechanistic details are the Baeyer-Villiger monooxygenases. Crystal structures and details on their kinetic mechanism have been unveiled for these powerful oxidative biocatalysts.
Fraaije has published almost 150 peer-reviewed papers with >8,000 citations; his h-index is 54 (Google Scholar). He was awarded a NWO VICI grant in 2016, was coordinator of the EU-FP7 project OXYGREEN, and coordinates the H2020-ITN OXYTRAIN training network. He was the main organizer of the 5th Novel Enzymes conference and is main organizer of the 19th International Flavins and Flavoproteins symposium.
Recent top publications
- Romero, E., Castellanos, J.R., Mattevi, A. & Fraaije, M.W. (2016) Characterization and Crystal Structure of a Robust Cyclohexanone Monooxygenase. Angew Chem Int Ed Engl. 55:15852-15855.
- Dijkman, W.P., Groothuis, D.E. & Fraaije, M.W. (2014) Enzyme-catalyzed oxidation of 5-hydroxymethylfurfural to furan-2,5-dicarboxylic acid. Angew Chem Int Ed Engl. 53:6515-6518.
- Brondani, P.B., Dudek, H.M., Martinoli, C., Mattevi, A. & Fraaije M.W. (2014) Finding the switch: turning a Baeyer-Villiger monooxygenase into a NADPH oxidase. J. Am. Chem. Soc. 136:16966-16969.