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

Autor: Rabuffetti M; Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy., Cannazza P; Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy., Contente ML; Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy., Pinto A; Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy., Romano D; Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy., Hoyos P; Department of Chemistry in Pharmaceutical Sciences (QUICIFARM), Pharmacy Faculty, Complutense University, Plaza de Ramon y Cajal, s/n, 28040 Madrid, Spain., Alcantara AR; Department of Chemistry in Pharmaceutical Sciences (QUICIFARM), Pharmacy Faculty, Complutense University, Plaza de Ramon y Cajal, s/n, 28040 Madrid, Spain., Eberini I; Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, Via Balzaretti 9, 20133 Milan, Italy., Laurenzi T; Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, Via Balzaretti 9, 20133 Milan, Italy., Gourlay L; Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milan, Italy., Di Pisa F; Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milan, Italy., 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.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2021 Mar; Vol. 108, pp. 104644. Date of Electronic Publication: 2021 Jan 11.
DOI: 10.1016/j.bioorg.2021.104644
Abstrakt: 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.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: