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-stereogenichydroxyesters 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.
CITATION STYLE
Oliveira, S. S. S., Bello, M. L., Rodrigues, C. R., De Azevedo, P. L., Ramos, M. C. K. V., De Aquino-Neto, F. R., … Dias, L. R. S. (2017). Asymmetric bioreduction of β-ketoesters derivatives by Kluyveromyces marxianus: Influence of molecular structure on the conversion and enantiomeric excess. Anais Da Academia Brasileira de Ciencias, 89(3), 1403–1415. https://doi.org/10.1590/0001-3765201720170118
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