CyBRiOx · Characterization and engineering of non-heme iron-dependent Rieske oxygenases involved in cyanobacterial indole alkaloid biosynthesis

Enzyme catalysis is a key technology at the heart of industrial biotechnology, which is expected to drive economic growth and industrial leadership in the EU, while effectively addressing social, environmental and economic needs. Despite the growing impact of biocatalysis, the full potential of this technology has yet to be realized. Major current limitations are: i) only a limited number of chemical reactions are amenable to biocatalysis, and ii) the unique enzymology encoded in the genome of organisms has been minimally explored. CyBRiOx will address this gap by elucidating the role of Rieske oxygenases (RiOx) in the late diversification pathway of indole alkaloids, a fascinating group of compounds with promising biological activities. In doing so, CyBRiOx will not only decipher the complete biosynthesis of these promising drug targets, but in parallel will develop novel RiOx biocatalysts catalyzing much-underdeveloped reaction classes in biocatalysis, namely CoA-independent desaturations and oxidative C-C bond formation reactions. This will be achieved by integrating knowledge of the natural activity of enzymes with bioinformatics, structural biology, enzyme engineering and organic synthesis to develop novel biocatalysts for highly underdeveloped reaction classes. Expanding the scope of existing RiOx offers tremendous potential for a cleaner, more selective, more efficient and therefore cheaper route to various key structural motifs relevant to the industrial and pharmaceutical industries. CyBRiOx will achieve this through the collaboration of the postdoctoral fellow with two leading experts in the field. The MSCA grant will allow the research fellow to further develop his scientific and transferable skills, expand his network, and enhance his overall career prospects and employability to become one of the next generation of leading scientists.