Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/224429
Share/Export:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Title

Fatty-Acid Oxygenation by Fungal Peroxygenases: From Computational Simulations to Preparative Regio- and Stereoselective Epoxidation

AuthorsMunicoy, Martí; González-Benjumea, Alejandro; Carro, Juan ; Aranda, Carmen; Linde, Dolores CSIC ORCID ; Renau-Mínguez, Chantal; Hofrichter, Martin; Guallar, Victor; Gutiérrez Suárez, Ana CSIC ORCID ; Martínez, Ángel T. CSIC ORCID
KeywordsAdaptive-PELE
Computational chemistry
Fungal unspecific peroxygenases
Monte Carlo molecular simulations
Oxygenation patterns
Regioselective epoxidation
Stereoselective epoxidation
Unsaturated fatty acids
Issue Date10-Nov-2020
PublisherAmerican Chemical Society
CitationACS Catalysis (10) 13584-13595 (2020)
AbstractEpoxidation of unsaturated fatty acids by unspecific peroxygenases (UPOs) of the best-known long-UPO subfamily, including the Agrocybe aegerita (AaeUPO) and Coprinopsis cinerea enzymes, is reported here. To understand the different oxygenation patterns by members of the long-UPO and short-UPO subfamilies, the latter represented by the Marasmius rotula enzyme (MroUPO), fatty-acid diffusion into their heme pockets was simulated with the adaptive PELE software. Computational results shed light on the inability of AaeUPO to epoxidize oleic acid (C18:1), opposed to MroUPO, due to steric hindrances to harbor (with a good interaction energy) the substrate with the Δ9 C10 atom at a catalytically relevant distance (<3.5 Å) from the oxo group in simulated heme compound-I. However, effective α-linolenic acid epoxidation is anticipated because the Δ15 C16 atom would attain such a distance in AaeUPO thanks to its more terminal position. The above hypothesis was verified using an engineered MroUPO variant (I153F/S156F) with a narrowed heme access channel mimicking that of AaeUPO. Experimental oxygenation of unsaturated fatty acids by this variant thus resembles that of AaeUPO, including regioselective (from 95% to >99%) formation of cis,cis-15,16-epoxyoctadeca-9,12-dienoic acid. The nearly complete conversion of α-linolenic acid by the two enzymes was transferred to a small preparative scale, the yield of purified product was estimated, its chemical structure analyzed by NMR, and more interestingly, stereoselective production of the 15(R),16(S) enantiomer (80-83% ee) assessed by chiral HPLC. This enzymatic synthesis overcomes the unspecificity of chemical epoxidation where the reaction cannot be restricted to the formation of monoepoxides as found during m-perchlorobenzoic acid oxidation of α-linolenic acid. Moreover, the variant was able to produce the unsaturated dicarboxylic fatty acid, together with subterminal oxygenation products, during partial conversion of oleic acid. These two noteworthy reactions had not been reported for any UPO described to date. © 2020 American Chemical Society. All rights reserved.
Description12 páginas.- 6 figuras.- 1 tabla.- 84 referencias.- The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acscatal.0c03165
Publisher version (URL)http://dx.doi.org/10.1021/acscatal.0c03165
URIhttp://hdl.handle.net/10261/224429
DOI10.1021/acscatal.0c03165
ISSN2155-5435
Appears in Collections:(IRNAS) Artículos
(CIB) Artículos

Files in This Item:
File Description SizeFormat
Fatty_Acid_oxygenation_fungal_2020.pdf6,49 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work

SCOPUSTM   
Citations

11
checked on May 11, 2022

WEB OF SCIENCETM
Citations

10
checked on May 16, 2022

Page view(s)

134
checked on May 16, 2022

Download(s)

79
checked on May 16, 2022

Google ScholarTM

Check

Altmetric

Dimensions


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.