9SZU

Cerium(III)-bound de novo photoredox enzyme (PLZ2.3)

Summary for 9SZU

• Entry DOI: 10.2210/pdb9szu/pdb
• Descriptor: PLZ2.3, CERIUM (III) ION, SODIUM ION, ... (4 entities in total)
• Functional Keywords: de novo protein, artificial metalloenzyme, cerium, photoenzyme
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 36749.10

Authors

Leiss-Maier, F.,Behringer, J.,Mustafa, G.,Heider, A.,Muehlhofer, R.,Klein, A.S.,Groll, M.,Zeymer, C. (deposition date: 2025-10-15, release date: 2026-03-25, Last modification date: 2026-06-03)

Primary citation

Leiss-Maier, F.,Behringer, J.,Mustafa, G.,Heider, A.,Muhlhofer, R.,Klein, A.S.,Groll, M.,Zeymer, C.
Computational redesign and directed evolution of a lanthanide-dependent photoredox enzyme for enantioselective diol cleavage.
Chem Sci, 17:9552-9561, 2026

PubMed Abstract: designed metalloenzymes and photoenzymes are a valuable addition to the biocatalytic toolbox. We previously introduced PhotoLanZymes (PLZ), a family of lanthanide-dependent photoredox enzymes that enable radical carbon-carbon bond cleavages of diol substrates upon Ce(iii/iv) binding and visible-light irradiation. While rational optimization increased their catalytic activity and photostability, the first generation of PLZ variants was limited by slow lanthanide binding and a lack of enantioselectivity. Here, we demonstrate that coupling computational redesign with directed evolution provides an effective strategy to overcome these limitations. First, we reduced the cavity size to enhance substrate interactions with the protein's active site, which facilitated initial enantiocontrol. Simultaneously, the AI-guided redesign approach improved the lanthanide binding kinetics. We then performed directed evolution to selectively accelerate the photocatalytic turnover for one of the substrate enantiomers, yielding a PLZ variant with markedly improved enantioselectivity. These results underscore the value of integrating AI-guided protein design with laboratory evolution to obtain stereoselective metalloenzymes and photoenzymes.

PubMed: 41883853
DOI: 10.1039/d5sc08010j

Experimental method

X-RAY DIFFRACTION (2.1 Å)