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Grant support

This work was supported by the European Union Project grant H2020-BBI-PPP-2015-2-720297-ENZOX2; the Spanish projects PID2019-106166RB-100-OXYWAVE, PID2020-118968RB-100-LILI, PID2021-123332OB-C21 and PID2019-107098RJ-I00, funded by the Ministerio de Ciencia e Innovacion/Agencia Estatal de Investigacion (AEI)/doi: 10.13039/501100011033/; the "Comunidad de Madrid" Synergy CAM project Y2018/BIO-4738-EVOCHIMERA-CM; the Generalitat Valenciana projects CIPROM/2021/079-PROMETEO and SEJI/2020/007; and the PIE-CSIC projects PIE-202040E185 and PIE-201580E042. P.G.d.S. thanks the Ministry of Science, Innovation and Universities (Spain) for her FPI scholarship (BES-2017-080040) and the Ministry of Science and Innovation for her contract as part of the PTQ2020-011037 project funded by MCIN/AEI/10.13039/501100011033 within the NextGenerationEU/PRTR. D.G.-P. thanks Juan de la Cierva Incorporacion contract Ref. No.: IJC2020-043725-I, funded by MCIN/AEI/10.13039/501100011033, and the EU NextGenerationEU/PRTR program. K.S. thanks to Ministerio de Ciencia e Innovacion and Fondo Social Europeo for a Ramon y Cajal contract (Ref. RYC2020-030596-I). We thank the Synchrotron Radiation Source at Alba (Barcelona, Spain) for assistance with the BL13-XALOC beamline.

Analysis of institutional authors

Mate, Diana MAuthor

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Article

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

Publicated to:Angewandte Chemie (International ed. Print). 62 (9): e202217372- - 2023-02-20 62(9), DOI: 10.1002/anie.202217372

Authors: de Santos, PG; Gonzalez-Benjumea, A; Fernandez-Garcia, A; Aranda, C; Wu, YQ; But, A; Molina-Espeja, P; Mate, DM; Gonzalez-Perez, D; Zhang, WY; Kiebist, J; Scheibner, K; Hofrichter, M; Swiderek, K; Moliner, V; Sanz-Aparicio, J; Hollmann, F; Gutierrez, A; Alcalde, M

Affiliations

Brandenburg Univ Technol Cottbus Senftenberg, Inst Biotechnol Inst, Univ Pl 1, D-01968 Senftenberg, Germany - Author
CSIC, Inst Catalysis, Dept Biocatalysis, C-Marie Curie 2, Madrid 28049, Spain - Author
CSIC, Inst Phys Chem Rocasolano, Dept Crystallog & Struct Biol, C-Serrano 119, Madrid 28006, Spain - Author
CSIC, Inst Recursos Nat & Agrobiol Sevilla IRNAS, Ave Reina Mercedes 10, Seville 41012, Spain - Author
Delft Univ Technol, Dept Biotechnol Inst, Maasweg St, 9, NL-2629 HZ Delft, Netherlands - Author
Evoenzyme SL, Parque Cientif Madrid, C-Faraday 7, Madrid 28049, Spain - Author
Tech Univ Dresden, Int Inst Zittau, Dept Bioand Environm Sci, Markt 23, D-02763 Zittau, Germany - Author
Univ Jaume 1, Inst Adv Mat INAM, BioComp Grp, Castellon de La Plana 12071, Spain - Author
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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 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.

Keywords

hydroxy fatty acidsover-oxidationprotein engineeringregioselectivityAliphatic-compoundsCurrent stateHydroxy fatty acidsOver-oxidationOxyfunctionalizationProtein engineeringRegioselectivityUnspecific peroxygenase

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Angewandte Chemie (International ed. Print) due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2023, it was in position 14/231, thus managing to position itself as a Q1 (Primer Cuartil), in the category Chemistry, Multidisciplinary. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 12.2, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-15, the following number of citations:

  • WoS: 11
  • Scopus: 30
  • OpenCitations: 21

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-15:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 51.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 51 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 10.
  • The number of mentions on the social network X (formerly Twitter): 15 (Altmetric).

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Germany; Netherlands.