| Structural highlights
7pna is a 1 chain structure with sequence from Cyclocybe aegerita. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.9Å |
| Ligands: | 7UT, CL, HEM, MG, NAG, PO4 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
APO1_CYCAE Aromatic peroxidase that oxidizes aryl alcohols into the corresponding aldehydes and then into the corresponding benzoic acids. Oxidizes toluene and naphthalene. Catalyzes the regioselective peroxide-dependent hydroxylation of propranolol and diclofenac to 5-hydroxypropranolol and 4'-hydroxydiclofenac. Catalyzes the regioselective peroxide-dependent hydroxylation of naphthalene to 1-naphthol or 2-naphthol via a naphthalene 1,2-oxide intermediate. Catalyzes the regioselective peroxide-dependent oxidation of pyridine to pyridine N-oxide. Halogenates monochlorodimedone and phenol. Oxidizes the sulfur-containing heterocycle dibenzothiophene to yield ring-hydroxylation products and to a lesser extent sulfoxidation products.[1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
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 omega-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 (omega-1)-hydroxytetradecanoic acid with 95 % regioselectivity and 83 % ee for the S enantiomer.
Engineering a Highly Regioselective Fungal Peroxygenase for the Synthesis of Hydroxy Fatty Acids.,Gomez de Santos P, Gonzalez-Benjumea A, Fernandez-Garcia A, Aranda C, Wu Y, But A, Molina-Espeja P, Mate DM, Gonzalez-Perez D, Zhang W, Kiebist J, Scheibner K, Hofrichter M, Swiderek K, Moliner V, Sanz-Aparicio J, Hollmann F, Gutierrez A, Alcalde M Angew Chem Int Ed Engl. 2023 Feb 20;62(9):e202217372. doi: , 10.1002/anie.202217372. Epub 2023 Jan 24. PMID:36583658[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ullrich R, Nuske J, Scheibner K, Spantzel J, Hofrichter M. Novel haloperoxidase from the agaric basidiomycete Agrocybe aegerita oxidizes aryl alcohols and aldehydes. Appl Environ Microbiol. 2004 Aug;70(8):4575-81. PMID:15294788 doi:https://dx.doi.org/10.1128/AEM.70.8.4575-4581.2004
- ↑ Ullrich R, Hofrichter M. The haloperoxidase of the agaric fungus Agrocybe aegerita hydroxylates toluene and naphthalene. FEBS Lett. 2005 Nov 7;579(27):6247-50. Epub 2005 Oct 19. PMID:16253244 doi:https://dx.doi.org/10.1016/j.febslet.2005.10.014
- ↑ Kluge MG, Ullrich R, Scheibner K, Hofrichter M. Spectrophotometric assay for detection of aromatic hydroxylation catalyzed by fungal haloperoxidase-peroxygenase. Appl Microbiol Biotechnol. 2007 Jul;75(6):1473-8. Epub 2007 Apr 5. PMID:17410351 doi:https://dx.doi.org/10.1007/s00253-007-0942-8
- ↑ Kluge M, Ullrich R, Dolge C, Scheibner K, Hofrichter M. Hydroxylation of naphthalene by aromatic peroxygenase from Agrocybe aegerita proceeds via oxygen transfer from H2O2 and intermediary epoxidation. Appl Microbiol Biotechnol. 2009 Jan;81(6):1071-6. doi: 10.1007/s00253-008-1704-y., Epub 2008 Sep 25. PMID:18815784 doi:https://dx.doi.org/10.1007/s00253-008-1704-y
- ↑ Ullrich R, Dolge C, Kluge M, Hofrichter M. Pyridine as novel substrate for regioselective oxygenation with aromatic peroxygenase from Agrocybe aegerita. FEBS Lett. 2008 Dec 10;582(29):4100-6. doi: 10.1016/j.febslet.2008.11.006. Epub, 2008 Nov 18. PMID:19022254 doi:https://dx.doi.org/10.1016/j.febslet.2008.11.006
- ↑ Aranda E, Kinne M, Kluge M, Ullrich R, Hofrichter M. Conversion of dibenzothiophene by the mushrooms Agrocybe aegerita and Coprinellus radians and their extracellular peroxygenases. Appl Microbiol Biotechnol. 2009 Apr;82(6):1057-66. doi:, 10.1007/s00253-008-1778-6. Epub 2008 Nov 28. PMID:19039585 doi:https://dx.doi.org/10.1007/s00253-008-1778-6
- ↑ Kinne M, Poraj-Kobielska M, Aranda E, Ullrich R, Hammel KE, Scheibner K, Hofrichter M. Regioselective preparation of 5-hydroxypropranolol and 4'-hydroxydiclofenac with a fungal peroxygenase. Bioorg Med Chem Lett. 2009 Jun 1;19(11):3085-7. doi: 10.1016/j.bmcl.2009.04.015. , Epub 2009 Apr 9. PMID:19394224 doi:https://dx.doi.org/10.1016/j.bmcl.2009.04.015
- ↑ Gomez de Santos P, González-Benjumea A, Fernandez-Garcia A, Aranda C, Wu Y, But A, Molina-Espeja P, Maté DM, Gonzalez-Perez D, Zhang W, Kiebist J, Scheibner K, Hofrichter M, Świderek K, Moliner V, Sanz-Aparicio J, Hollmann F, Gutiérrez A, Alcalde M. Engineering a Highly Regioselective Fungal Peroxygenase for the Synthesis of Hydroxy Fatty Acids. Angew Chem Int Ed Engl. 2023 Feb 20;62(9):e202217372. PMID:36583658 doi:10.1002/anie.202217372
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