7PN6

Evolved unspecific peroxygenase with A77L mutation in complex with myristic acid

Summary for 7PN6

• Entry DOI: 10.2210/pdb7pn6/pdb
• Related: 5OXU 7PN4 7PN5
• Descriptor: Aromatic peroxygenase, MYRISTIC ACID, MAGNESIUM ION, ... (8 entities in total)
• Functional Keywords: myristic acid complex, peroxygenase, peroxidase, oxidoreductase
• Biological source: Agrocybe aegerita (Black poplar mushroom, Agaricus aegerita)
• Total number of polymer chains: 1
• Total formula weight: 38095.64

Authors

Fernandez-Garcia, A.,Sanz-Aparicio, J. (deposition date: 2021-09-06, release date: 2023-01-25, Last modification date: 2024-02-07)

Primary citation

Gomez de Santos, P.,Gonzalez-Benjumea, A.,Fernandez-Garcia, A.,Aranda, C.,Wu, Y.,But, A.,Molina-Espeja, P.,Mate, D.M.,Gonzalez-Perez, D.,Zhang, W.,Kiebist, J.,Scheibner, K.,Hofrichter, M.,Swiderek, K.,Moliner, V.,Sanz-Aparicio, J.,Hollmann, F.,Gutierrez, A.,Alcalde, M.
Engineering a Highly Regioselective Fungal Peroxygenase for the Synthesis of Hydroxy Fatty Acids.
Angew.Chem.Int.Ed.Engl., 62:e202217372-e202217372, 2023

PubMed 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 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.

PubMed: 36583658
DOI: 10.1002/anie.202217372

Experimental method

X-RAY DIFFRACTION (1.5 Å)