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MetRaZymes: Metal-containing Radical Enzymes

Lead Research Organisation: University of Strathclyde
Department Name: Pure and Applied Chemistry

Abstract

The pharmaceutical, chemical and polymer industries are cornerstones of Europe's economy. A key element for their transition to more sustainable processes and to innovative new compounds is biocatalysis. 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. To develop novel biocatalysts, a highly interdisciplinary skill set is needed. MetRaZymes will create a PhD school across leading European universities that will train 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 metalloenzymes as the focal point, the ESRs will develop novel biocatalysts for radical reactions of high synthetic value, such as the late stage modification of pharmaceutical intermediates or the synthesis of polymers from renewable monomers. To train the ESRs in the needs of industrial biotechnology, the consortium includes eight of Europe's leading pharmaceutical, chemical and enzymology companies. The ESRs will 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 will act as muliplicators for the communication of results. Moreover, the ESRs will work with artist that use biology as their way of expression to create an ARTzymes exhibition that will foster the ERS's creativity and result in a an unique form of science dialogue with the general public

Publications

10 25 50
 
Description The project is still ongoing, but at this interim stage the following key findings can be identified. The most significant achievement from the award so far has been the use of molecular simulation to help understand the structure, dynamics and function of an artificial metalloenzyme that is being developed to catalyse new to nature reactions for industrial applications. A database of artificial metalloenzymes and the reactions they catalyse has also been created, from which several machine learning algorithms have been developed to help model their catalytic behaviour. Combining molecular simulation and machine learning is allowing us to investigate artificial metalloenzymes in the computer and suggest design strategies prior to synthesis and testing. We are on course to meet the objectives of the awards. The best course of action to take the findings forward will be decided towards the end of the project when the final results are known, but it is likely to involve further academic study and some knowledge transfer to industrial partners in the network.
Exploitation Route The best course of action to take the findings forward will be decided towards the end of the project when the final results are known, but it is likely to involve further academic study and some knowledge transfer to industrial partners in the network.
Sectors Agriculture

Food and Drink

Chemicals

Environment

Healthcare

Manufacturing

including Industrial Biotechology

Pharmaceuticals and Medical Biotechnology

 
Title A Database of Artificial Metalloenzymes 
Description A Database of Artificial Metalloenzymes that links experimental structures (e.g. X-ray crystal, NMR) and reaction data (e.g. conditions, reactants/products, yield, enantioselectivity, etc) compiled from the peer-reviewed literature. 
Type Of Material Database/Collection of data 
Year Produced 2025 
Provided To Others? No  
Impact The database is still under development, but it has reached a sufficient size to train AI models that will be used in computer-aided design of artificial metalloenzymes. A first version of the database has been shared with other researchers in the MetRaZymes network. Feedback from that process will be used to improve the database, which will be released publicly towards the end of the project. 
 
Description Affiliated Member of MSCA Doctoral Training Network in Metal-Containing Radical Enzymes ("MetRaZymes") 
Organisation Technical University of Darmstadt
Country Germany 
Sector Academic/University 
PI Contribution The doctoral candidate, Ilayda Tolu, who is funded by this grant is an affiliated member of the MSCA Doctoral Training Network in Metal-Containing Radical Enzymes ("MetRaZymes"), has allowed her to take part in all research and training activities of the network. Since starting work in September 2023, Ilayda has contributed to the following network activities: 1. MetRaZymes First Annual Network Meeting - two days of research presentations and workshops at Technical University of Darmstadt in Germany from 28th-29th September 2023. 2. MetRaZymes First Doctoral Candidate Training Sessions - a week of specialist doctoral training workshops and courses at Technical University of Darmstadt in Germany from 2nd-6th October 2023. Training sessions were delivered by both University and external providers including a workshop on scientific publication run by the Nature Publishing group. 3. Monthly MetRaZymes Online Doctoral Meet Ups - regular meetings of all doctoral candidates in the network (across 12 universities in the UK and mainland Europe)
Collaborator Contribution Metal-containing radical enzymes creates a PhD school 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. Led by Prof Nico Bruns at the Technical University of Darmstadt, and supported by 12 Universities across the UK and mainland Europe, the network collectively create an exceptional doctoral training experience to create a new generation of experts in this exciting field.
Impact No outputs yet.
Start Year 2023
 
Description Research visit: Ilayda Tolu visiting the group of Prof Gerard Roelfes at the University of Groningen 
Organisation University of Groningen
Country Netherlands 
Sector Academic/University 
PI Contribution Ilayda Tolu, the doctoral candidate affiliated with the MetRaZymes MSCA Doctoral Training Network, has begun working with members of Prof Gerard Roelfes group at the University of Groningen. She will visit Groningen for one month in March 2024 to further research collaborations.
Collaborator Contribution Prof Gerard Roelfes group at the University of Groningen will provide training in experimental methods for designing and optimising artificial metalloenzymes.
Impact This is a multi-disciplinary collaboration between experimental and computational biochemistry groups.
Start Year 2023
 
Description An invited talk at EPIC conference at University Hospital in Antwerp. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact An invited talk at EPIC conference at University Hospital in Antwerp.
Year(s) Of Engagement Activity 2023
 
Description Invited talk at BiotechX conferences 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact I gave an invited talk to PhD students, postdocs, academics and industrial scientistis at the BiotechX 2023 conferences in Basel, Switzerland.
Year(s) Of Engagement Activity 2023
URL https://www.terrapinn.com/conference/biotechx/index.stm
 
Description Talk at University of Darmstadt 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact I gave at talk to PhD students, academics and industry scientists at the University of Darmstadt about computational methods to optimise artificial metalloenzymes
Year(s) Of Engagement Activity 2023
URL https://metrazymes.eu/