Unspecific peroxygenases (UPOs) catalyze the selective oxygenation of organic substrates using only hydrogen peroxide as the oxidant. In particular, the PaDa-I variant of the UPO from Agrocybe aegerita has been shown to oxidize Z- and E-allylic alcohols with complementary selectivity, giving epoxide products from Z-isomers (with excellent enantioselectivity, >99 % ee) and carboxylic acid/aldehyde products from E-isomers.

In this collaboration study, computational studies combining quantum mechanics and molecular dynamics were used to determine some reaction species and rationalize the experimentally observed divergent selectivity. Density functional theory (DFT) calculations were employed to characterize the epoxidation and carboxylation pathways for both Z- and E-allylic alcohols, which combined with unrestrained Molecular Dynamics (MD) simulations considering the RC obtained from the DFT calculations revealed that active site pocket of rAaeUPO-PaDa-I-H favors a different binding of the allylic alcohol depending on the E/Z configuration, yielding selective divergent oxidation products. These computational insights not only corroborate the experimental observations but also emphasize the importance of active site conformational dynamics in substrate binding and divergent reactivity.

It has been recently published open access in Angewandte Chemie International Edition:
J. Li, C. Duran, B. Pogrányi, K. A. S. Cornish, J. Cartwright, S. Osuna*,  W. P. Unsworth*, G. Grogan*
“Divergent Oxidation Reactions of E- and Z-Allylic Primary Alcohols by an Unspecific Peroxygenase“
Angew. Chem. Int. Ed.., 2025, e202422241
DOI: 10.1002/anie.202422241

Girona, February 18th, 2024
For more info: ges.iqcc@udg.edu