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- Title
Engineering a Highly Regioselective Fungal Peroxygenase for the Synthesis of Hydroxy Fatty Acids.
- Authors
Gomez de Santos, Patricia; González‐Benjumea, Alejandro; Fernandez‐Garcia, Angela; Aranda, Carmen; Wu, Yinqi; But, Andrada; Molina‐Espeja, Patricia; Maté, Diana M.; Gonzalez‐Perez, David; Zhang, Wuyuan; Kiebist, Jan; Scheibner, Katrin; Hofrichter, Martin; Świderek, Katarzyna; Moliner, Vicent; Sanz‐Aparicio, Julia; Hollmann, Frank; Gutiérrez, Ana; Alcalde, Miguel
- Abstract
The hydroxylation of fatty acids is an appealing reaction in synthetic chemistry, although the lack of selective catalysts hampers its industrial implementation. In this study, we have engineered a highly regioselective fungal peroxygenase for the ω‐1 hydroxylation of fatty acids with quenched stepwise over‐oxidation. One single mutation near the Phe catalytic tripod narrowed the heme cavity, promoting a dramatic shift toward subterminal hydroxylation with a drop in the over‐oxidation activity. While crystallographic soaking experiments and molecular dynamic simulations shed light on this unique oxidation pattern, the selective biocatalyst was produced by Pichia pastoris at 0.4 g L−1 in a fed‐batch bioreactor and used in the preparative synthesis of 1.4 g of (ω‐1)‐hydroxytetradecanoic acid with 95 % regioselectivity and 83 % ee for the S enantiomer.
- Subjects
HYDROXY acids; FATTY acids; ENANTIOMERS; CHEMICAL reactions; PICHIA pastoris; DYNAMIC simulation
- Publication
Angewandte Chemie, 2023, Vol 135, Issue 9, p1
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.202217372