Artificial Lanthanide Enzymes for Selective Photocatalysis: 'Enlightening' Metalloenzyme Design and Evolution

Informacje na temat projektu

PhotoLanZyme

Identyfikator umowy o grant: 101039592

DOI

10.3030/101039592

Data podpisania przez KE 11 Kwietnia 2022

Data rozpoczęcia 1 Maja 2022

Data zakończenia 30 Kwietnia 2027

Finansowanie w ramach

• European Research Council (ERC)

Koszt całkowity

€ 1 500 000,00

Wkład UE

€ 1 500 000,00

Koordynowany przez

TECHNISCHE UNIVERSITAET MUENCHEN
Germany

Periodic Reporting for period 1 - PhotoLanZyme (Artificial Lanthanide Enzymes for Selective Photocatalysis: 'Enlightening' Metalloenzyme Design and Evolution)

Okres sprawozdawczy: 2022-05-01 do 2024-10-31

Podsumowanie kontekstu i ogólnych celów projektu

The chemical and pharmaceutical industry is under increasing pressure to complement traditional chemical catalysis with sustainable biocatalytic approaches. Enzymes enable such green chemistry. In many cases, however, they do not promote the non-natural reactions relevant for industrial processes. It thus remains a major challenge to develop novel biocatalysts for chemical reactions beyond nature’s synthetic repertoire. PhotoLanZyme addresses this problem with a fundamentally new strategy, which combines metal-dependent chemical photoredox catalysis with enzyme engineering.
Photoexcitation is a powerful catalytic trigger that facilitates single electron transfer processes inaccessible in the dark. However, the reactive radical species generated in these reactions are difficult to control, which often leads to low regio- and stereoselectivity. We propose to tackle this key challenge in synthetic chemistry by performing photoredox catalysis in de novo designed metalloproteins, which can be optimized efficiently by laboratory evolution. These proteins will not only coordinate the photocatalytic metal ion, but also provide well-defined binding interactions in a chiral environment to control reactive intermediates. Specifically, we aim to implement lanthanide-dependent photoredox chemistry in proteins, which will yield a new class of sustainable photobiocatalysts for stereoselective C–H activation and C–C bond forming reactions.

Prace wykonane od początku projektu do końca okresu sprawozdawczego oraz najważniejsze dotychczasowe rezultaty

In the first two years since the start of the project, a team of PhD students and postdocs with diverse background in biochemistry, synthetic organic chemistry, protein engineering, and computational modeling has been working on the development of the first de novo enzyme for cerium photoredox catalysis. We demonstrated proof of concept using a computationally designed protein scaffold with a high-affinity lanthanide binding site. The protein catalyzes a radical carbon-carbon bond cleavage in the presence of cerium(III) chloride and visible light. We could improve the catalyst's photostability via rational engineering and established whole-cell photobiocatalysis. For the latter, the photoenzyme is displayed on the surface of E. coli cells. Furthermore, we developed a luminescence-based assay to identify potent lanthanide binders from protein scaffold libraries.

Innowacyjność oraz oczekiwany potencjalny wpływ (w tym dotychczasowe znaczenie społeczno-gospodarcze i szersze implikacje społeczne projektu)

We are currently focusing on expanding the scope towards more challenging reactions, improving the system's stereoselectivity, and implementing a powerful in vivo selection strategy.

PhotoLanZyme in a nutshell