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.
Structural insights into the desymmetrization of bulky 1,2-dicarbonyls through enzymatic monoreduction / M. Rabuffetti, P. Cannazza, M.L. Contente, A. Pinto, D. Romano, P. Hoyos, A.R. Alcantara, I. Eberini, T. Laurenzi, L. Gourlay, F. Di Pisa, F. Molinari. - In: BIOORGANIC CHEMISTRY. - ISSN 0045-2068. - 108(2021 Mar), pp. 104644.1-104644.7.
|Titolo:||Structural insights into the desymmetrization of bulky 1,2-dicarbonyls through enzymatic monoreduction|
MOLINARI, FRANCESCO ENZO (Corresponding)
|Parole Chiave:||biocatalysis; crystal structure; enzymatic reduction; in silico analysis; ketoreductase; pichia glucozyma|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||mar-2021|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.bioorg.2021.104644|
|Appare nelle tipologie:||01 - Articolo su periodico|