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Metal-containing Radical Enzymes

Periodic Reporting for period 1 - MetRaZymes (Metal-containing Radical Enzymes)

Reporting period: 2022-10-01 to 2024-09-30

The pharmaceutical, chemical, and polymer industries are cornerstones of Europe’s economy. Biocatalysis is a key element in their transition to more sustainable processes and innovative new compounds. Of particular interest are metallo-enzymes, i.e. proteins that host a metal cofactor. They catalyze a multitude of redox and radical reactions. To access reactions that are unknown in nature, artificial metallo-enzymes can be created. They combine the new-to-nature catalytic activity of metal complexes with the selectivity-inducing environment of the active protein site. Biocatalysis of radical processes is at the heart of many biotransformations, including stereoselective synthesis for the production of pharmaceuticals, late-stage functionalization and diversification of pharmaceutical compounds, and the synthesis of polymeric materials. In order to develop novel biocatalytic routes in academia and industry, a highly interdisciplinary skill set is needed that ranges from chemistry to protein engineering and bioprocess engineering.
MetRaZymes is a PhD research and training programme across leading European universities that trains the next generation of scientists capable of tackling the design, development, and implementation of novel enzymatic reactions in a holistic approach. It brings together computational bioscientists, bioinorganic and polymer chemists, and bioprocess engineers. Using artificial and repurposed natural metalloenzymes as the focal point, the Doctoral Candidates develop novel biocatalysts by computational and experimental methods for radical reactions of high synthetic value, such as the late-stage modification of pharmaceutical intermediates, regio-selective functionalizations of aromatic groups in drug molecules, radical atom transfer addition reactions to unsaturated double bonds, radical polymerizations, or the synthesis of polymers from renewable monomers. Moreover, processes to produce the novel enzymes on a larger scale and to run the biotransformations in advanced reactors are being developed.
To train the Doctoral Candidates in the needs of industrial biotechnology, the consortium includes eight of Europe´s leading pharmaceutical, chemical, and enzymology companies. The Doctoral Candidates benefit from a vast transferable skills training program delivered by five training partners. Highlights include a Nature Masterclass and Wikipedia workshop. Communication partners such as Wikimedia and the Industrial Biotechnology Innovation Centre act as multiplicators for the communication of results. Moreover, the Doctoral Candidates will work with artists who use biology as their way of expression to create an ARTzymes exhibition that will foster the Doctoral Candidates' creativity and result in a unique form of science dialogue with the general public.
The work in MetRaZymes is well underway, and results will be revealed once the first publications have been published.
The work in MetRaZymes is well underway, and results will be revealed once the first publications have been published.
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