Title |
Asymmetric bioreduction of β-ketoesters derivatives by Kluyveromyces marxianus: influence of molecular structure on the conversion and enantiomeric excess
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Published in |
Anais da Academia Brasileira de Ciências, September 2017
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DOI | 10.1590/0001-3765201720170118 |
Pubmed ID | |
Authors |
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 |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 14 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Professor | 4 | 29% |
Student > Ph. D. Student | 3 | 21% |
Student > Bachelor | 2 | 14% |
Other | 1 | 7% |
Unknown | 4 | 29% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 2 | 14% |
Chemistry | 2 | 14% |
Agricultural and Biological Sciences | 1 | 7% |
Chemical Engineering | 1 | 7% |
Immunology and Microbiology | 1 | 7% |
Other | 1 | 7% |
Unknown | 6 | 43% |