Asymmetric bioreduction of β-ketoesters derivatives by Kluyveromyces marxianus: influence of molecular structure on the conversion and enantiomeric excess
| Autor: | SIMONE S.S. OLIVEIRA, MURILO L. BELLO, CARLOS R. RODRIGUES, PAULA L. DE AZEVEDO, MARIA C.K.V. RAMOS, FRANCISCO R. DE AQUINO-NETO, SORELE B. FIAUX, LUIZA R.S. DIAS |
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| Jazyk: | angličtina |
| Předmět: | |
| Zdroj: | Anais da Academia Brasileira de Ciências, Iss 0 |
| Druh dokumentu: | article |
| ISSN: | 1678-2690 0001-3765 |
| DOI: | 10.1590/0001-3765201720170118 |
| Popis: | ABSTRACT This study presents the bioreduction of six β-ketoesters by whole cells of Kluyveromyces marxianus and molecular investigation of a series of 13 β-ketoesters by hologram quantitative structure-activity relationship (HQSAR) in order to relate with conversion and enantiomeric excess of β-stereogenic-hydroxyesters obtained by the same methodology. Four of these were obtained as (R)-configuration and two (S)-configuration, among them four compounds exhibited >99% enantiomeric excess. The β-ketoesters series LUMO maps showed that the β-carbon of the ketoester scaffold are exposed to undergo nucleophilic attack, suggesting a more favorable β-carbon side to enzymatic reduction based on adopted molecular conformation at the reaction moment. The HQSAR method was performed on the β-ketoesters derivatives separating them into those provided predominantly (R)- or (S)-β-hydroxyesters. The HQSAR models for both (R)- and (S)-configuration showed high predictive capacity. The HQSAR contribution maps suggest the importance of β-ketoesters scaffold as well as the substituents attached therein to asymmetric reduction, showing a possible influence of the ester group carbonyl position on the molecular conformation in the enzyme catalytic site, exposing a β-carbon side to the bioconversion to (S)- and (R)-enantiomers. |
| Databáze: | Directory of Open Access Journals |
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