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Stereodivergent photobiocatalytic radical cyclization through the repurposing and directed evolution of fatty acid photodecarboxylases.
- Source :
-
Nature chemistry [Nat Chem] 2024 Aug; Vol. 16 (8), pp. 1339-1347. Date of Electronic Publication: 2024 Apr 17. - Publication Year :
- 2024
-
Abstract
- Despite their intriguing photophysical and photochemical activities, naturally occurring photoenzymes have not yet been repurposed for new-to-nature activities. Here we engineered fatty acid photodecarboxylases to catalyse unnatural photoredox radical C-C bond formation by leveraging the strongly oxidizing excited-state flavoquinone cofactor. Through genome mining, rational engineering and directed evolution, we developed a panel of radical photocyclases to facilitate decarboxylative radical cyclization with excellent chemo-, enantio- and diastereoselectivities. Our high-throughput experimental workflow allowed for the directed evolution of fatty acid photodecarboxylases. An orthogonal set of radical photocyclases was engineered to access all four possible stereoisomers of the stereochemical dyad, affording fully diastereo- and enantiodivergent biotransformations in asymmetric radical biocatalysis. Molecular dynamics simulations show that our evolved radical photocyclases allow near-attack conformations to be easily accessed, enabling chemoselective radical cyclization. The development of stereoselective radical photocyclases provides unnatural C-C-bond-forming activities in natural photoenzyme families, which can be used to tame the stereochemistry of free-radical-mediated reactions.<br /> (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
- Subjects :
- Cyclization
Stereoisomerism
Free Radicals chemistry
Free Radicals metabolism
Photochemical Processes
Molecular Dynamics Simulation
Fatty Acids chemistry
Fatty Acids metabolism
Directed Molecular Evolution
Deoxyribodipyrimidine Photo-Lyase metabolism
Deoxyribodipyrimidine Photo-Lyase chemistry
Biocatalysis
Subjects
Details
- Language :
- English
- ISSN :
- 1755-4349
- Volume :
- 16
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Nature chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 38632367
- Full Text :
- https://doi.org/10.1038/s41557-024-01494-0