Computational rational design of unspecific peroxygenase for C-H oxidation

Science Advances 2026 Open access

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Authors: Ruichen Gao, Xiaodi Fu, Zonglin Li, Zheng Wang, Zhiyao Wang, Guanjian Li, Jun Ge, Frank Hollmann, Zhanfeng Wang, Zhanfeng Wang, Wen‐Yong Lou, Xiaoling Wu
DOI: 10.1126/sciadv.aeb6329
Cited by: 7
References: 56

Abstract

Computational rational design has emerged as a transformative approach to engineer enzymes with tailored selectivity and efficiency. In the context of carbon-hydrogen oxidation, a key challenge in synthetic chemistry, unspecific peroxygenases (UPOs) directly oxidize unactivated carbon-hydrogen bonds using hydrogen peroxide, yet their utility is limited by low activity and imperfect selectivity. By computational rational design, this study systematically navigated vast sequence spaces to identify mutations that enhance catalytic performance of UPOs, lastly yielded UPO variants with 13-fold enhanced activity and >99% enantioselectivity, and revealed the dominant role of residue Lys 165 in activity and enantioselectivity. This study shows how computational strategies overcome evolutionary constraints to deliver efficient biocatalysts for synthetic chemistry.

Fields of Study & Subjects

Enzyme Catalysis and Immobilization Metal-Catalyzed Oxygenation Mechanisms Enzyme-mediated dye degradation

Publication details

Journal / source
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Volume
12
Issue
5
Pages
eaeb6329–eaeb6329
Publication date
30 January 2026
Language
EN