9ORN

Structure of the Acinetobacter calcoaceticus Cyclohexanone Monooxygenase mutant M10-R327K-R490E-I491E-Y246F-S186W-T187V

Summary for 9ORN

• Entry DOI: 10.2210/pdb9orn/pdb
• Descriptor: Putative flavin-binding monooxygenase, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: cyclohexanone monooxygenase, fad binding, oxidoreductase, acinetobacter calcoaceticus
• Biological source: Acinetobacter calcoaceticus
• Total number of polymer chains: 1
• Total formula weight: 62101.71

Authors

Raps, F.C.,Jeffrey, P.D.,Sorigue, D.,Hyster, T.K. (deposition date: 2025-05-22, release date: 2025-09-03, Last modification date: 2025-11-19)

Primary citation

Raps, F.C.,Jin, C.A.,Brown, A.C.,Sorigue, D.,Hyster, T.K.
Stereoselective Photoenzymatic Hydroarylation for the Construction of Quaternary Stereocenters.
J.Am.Chem.Soc., 147:40547-40553, 2025

PubMed Abstract: Quaternary carbon stereocenters are a crucial component of many bioactive molecules, but they can be challenging to prepare stereoselectively. Olefin hydroarylations are an attractive means for preparing this motif; however, existing methods struggle to set stereocenters on substrates lacking traditional catalyst binding handles. Here, we report a stereoselective photoenzymatic olefin hydroarylation using a repurposed Baeyer-Villiger monooxygenase. Three rounds of iterative site-saturation mutagenesis yielded a photoenzyme capable of preparing valuable tetrahydroquinolines in high yields with excellent enantioselectivity. The engineered variant accepts various arene substituents, highlighting the synthetic utility of this methodology. DFT calculations and control experiments suggest that the protein templates a through-space interaction between the tertiary radical and aromatic group, which attenuates the oxidation potential of the radical, enabling C-C bond formation.

PubMed: 41133312
DOI: 10.1021/jacs.5c12440

Experimental method

X-RAY DIFFRACTION (1.75 Å)