Structural insights into the desymmetrization of bulky 1,2-dicarbonyls through enzymatic monoreduction.

Biocatalysis Crystal structure Enzymatic reduction In silico analysis Ketoreductase Pichia glucozyma

Journal

Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703

Informations de publication

Date de publication:
03 2021
Historique:
received: 28 12 2020
revised: 05 01 2021
accepted: 06 01 2021
pubmed: 25 1 2021
medline: 1 10 2021
entrez: 24 1 2021
Statut: ppublish

Résumé

Benzil reductases are dehydrogenases preferentially active on aromatic 1,2-diketones, but the reasons for this peculiar substrate recognition have not yet been clarified. The benzil reductase (KRED1-Pglu) from the non-conventional yeast Pichia glucozyma showed excellent activity and stereoselectivity in the monoreduction of space-demanding aromatic 1,2-dicarbonyls, making this enzyme attractive as biocatalyst in organic chemistry. Structural insights into the stereoselective monoreduction of 1,2-diketones catalyzed by KRED1-Pglu were investigated starting from its 1.77 Å resolution crystal structure, followed by QM and classical calculations; this study allowed for the identification and characterization of the KRED1-Pglu reactive site. Once identified the recognition elements involved in the stereoselective desymmetrization of bulky 1,2-dicarbonyls mediated by KRED1-Pglu, a mechanism was proposed together with an in silico prediction of substrates reactivity.

Identifiants

pubmed: 33486371
pii: S0045-2068(21)00020-1
doi: 10.1016/j.bioorg.2021.104644
pii:
doi:

Substances chimiques

Aldehydes 0
Alcohol Oxidoreductases EC 1.1.-
benzil reductase EC 1.1.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

104644

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Auteurs

Marco Rabuffetti (M)

Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy.

Pietro Cannazza (P)

Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy.

Martina Letizia Contente (ML)

Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy.

Andrea Pinto (A)

Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy.

Diego Romano (D)

Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy.

Pilar Hoyos (P)

Department of Chemistry in Pharmaceutical Sciences (QUICIFARM), Pharmacy Faculty, Complutense University, Plaza de Ramon y Cajal, s/n, 28040 Madrid, Spain.

Andres R Alcantara (AR)

Department of Chemistry in Pharmaceutical Sciences (QUICIFARM), Pharmacy Faculty, Complutense University, Plaza de Ramon y Cajal, s/n, 28040 Madrid, Spain.

Ivano Eberini (I)

Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, Via Balzaretti 9, 20133 Milan, Italy.

Tommaso Laurenzi (T)

Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, Via Balzaretti 9, 20133 Milan, Italy.

Louise Gourlay (L)

Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milan, Italy.

Flavio Di Pisa (F)

Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milan, Italy.

Francesco Molinari (F)

Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy. Electronic address: francesco.molinari@unimi.it.

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Classifications MeSH