A team led by Prof. Cathleen Zeymer from TUM has now introduced a new class of designer enzymes that use a lanthanide cofactor and are activated by light. These enzymes have been dubbed "PhotoLanZymes".
Computational modeling and experimental work are combined successfully: The protein scaffold of these enzymes has been designed on a computer, but it can be produced by bacteria in the lab. Inside the protein is a metal-binding site for cerium ions. Cerium belongs to the lanthanides, which are also known as rare earth elements. However, cerium is not as rare as it might seem and is about as abundant in the Earth's crust as copper. According to Prof. Zeymer, “Complexes of cerium can be used as photoredox catalysts, meaning they harness the energy of light to enable a variety of radical reactions.” This non-natural chemistry has now been realized in the context of an enzyme for the first time.
The designer enzyme was initially optimized for the radical cleavage of carbon-carbon bonds but is also intended to be used for the reverse reaction in the future, that is, the selective formation of new bonds. To achieve this, Prof. Zeymer and her team are actively working on these developments, employing both computer-aided protein design and directed evolution in the lab. Additionally, whole bacterial cells can be used as photo-biocatalysts when the enzyme is displayed on their surface, allowing for even more resource-efficient use in practice.
The research results achieved here lay the foundation for the development of a new class of photoenzymes with broad application potential for the more sustainable production of complex molecules, such as pharmaceutical compounds.
Publication:
Klein AS, Leiss-Maier F, Mühlhofer R et al. A de novo metalloenzyme for cerium photoredox catalysis. J. Amer. Chem. Soc. (2024) DOI: 10.1021/jacs.4c04618
https://pubs.acs.org/doi/full/10.1021/jacs.4c04618
Funding:
This work is funded by an ERC Starting Grant (“PhotoLanZyme” 101039592). https://www.tum.de/en/news-and-events/all-news/press-releases/details/eu-foerderung-fuer-fuenf-forschungsprojekte
Additional Links:
As part of the CRC/Transregio 325 “Assembly Controlled Chemical Photocatalysis”, Prof. Zeymer’s team is working with colleagues from TUM and the University of Regensburg on further light-dependent enzymes for biocatalysis. https://crc325.de/
Prof. Zeymer’s laboratory can be found at Center for Functional Protein Assemblies (CPA). https://www.cpa.tum.de/cpa/home/
The research group is also associated with the TUM Catalysis Research Center. https://www.crc.tum.de/crc/home/
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