Details

Autor(en) / Beteiligte

• 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

Titel

Engineering a Highly Regioselective Fungal Peroxygenase for the Synthesis of Hydroxy Fatty Acids

Ist Teil von

• Angewandte Chemie International Edition, 2023-02, Vol.62 (9), p.e202217372-n/a

Auflage

International ed. in English

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. The biocatalytic hydroxylation of fatty acids is an appealing reaction, but the generation of over‐oxidation by‐products and the lack of selectivity hampers its transfer to industry. Now a highly selective and efficient peroxygenase has been engineered for the production of hydroxy fatty acids through a synthetic procedure that can be rapidly adapted to the preparative scale.