@misc{GomezdeSantosGonzalezBenjumeaFernandezGarciaetal., author = {Gomez de Santos, Patricia and Gonz{\´a}lez-Benjumea, Alejandro and Fernandez-Garcia, Angela and Aranda, Carmen and Wu, Yinqi and But, Andrada and Molina-Espeja, Patricia and Mat{\´e}, Diana M. and Gonzalez-Perez, David and Zhang, Wuyuan and Kiebist, Jan and Scheibner, Katrin and Hofrichter, Martin and Swiderek, Katarzyna and Moliner, Vicent and Sanz-Aparicio, Julia and Hollmann, Frank and Guti{\´e}rrez, Ana and Alcalde, Miguel}, title = {Engineering a highly regioselective fungal peroxygenase for the synthesis of hydroxy fatty acids}, series = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker}, volume = {62}, journal = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1521-3773}, doi = {10.1002/anie.202217372}, pages = {1 -- 9}, 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.}, language = {en} }