Asymmetric bioreduction of β-ketoesters derivatives by Kluyveromyces marxianus: influence of molecular structure on the conversion and enantiomeric excess
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-ster...
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| Format: | Article |
| Language: | English |
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Academia Brasileira de Ciências
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| Series: | Anais da Academia Brasileira de Ciências |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652017005017104&lng=en&tlng=en |
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| author | 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 |
| author_facet | 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 |
| author_sort | SIMONE S.S. OLIVEIRA |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T15:56:33Z |
| format | Article |
| id | doaj.art-6345130ea2a244668eafbc4bc0c0f902 |
| institution | Directory Open Access Journal |
| issn | 1678-2690 |
| language | English |
| last_indexed | 2024-12-13T15:56:33Z |
| publisher | Academia Brasileira de Ciências |
| record_format | Article |
| series | Anais da Academia Brasileira de Ciências |
| spelling | doaj.art-6345130ea2a244668eafbc4bc0c0f9022022-12-21T23:39:18ZengAcademia Brasileira de CiênciasAnais da Academia Brasileira de Ciências1678-2690010.1590/0001-3765201720170118S0001-37652017005017104Asymmetric bioreduction of β-ketoesters derivatives by Kluyveromyces marxianus: influence of molecular structure on the conversion and enantiomeric excessSIMONE S.S. OLIVEIRAMURILO L. BELLOCARLOS R. RODRIGUESPAULA L. DE AZEVEDOMARIA C.K.V. RAMOSFRANCISCO R. DE AQUINO-NETOSORELE B. FIAUXLUIZA R.S. DIASABSTRACT 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652017005017104&lng=en&tlng=enbiocatalysisβ-ketoestersβ-hydroxyestersHQSARwhole cell bioreduction |
| spellingShingle | 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 Asymmetric bioreduction of β-ketoesters derivatives by Kluyveromyces marxianus: influence of molecular structure on the conversion and enantiomeric excess Anais da Academia Brasileira de Ciências biocatalysis β-ketoesters β-hydroxyesters HQSAR whole cell bioreduction |
| title | Asymmetric bioreduction of β-ketoesters derivatives by Kluyveromyces marxianus: influence of molecular structure on the conversion and enantiomeric excess |
| title_full | Asymmetric bioreduction of β-ketoesters derivatives by Kluyveromyces marxianus: influence of molecular structure on the conversion and enantiomeric excess |
| title_fullStr | Asymmetric bioreduction of β-ketoesters derivatives by Kluyveromyces marxianus: influence of molecular structure on the conversion and enantiomeric excess |
| title_full_unstemmed | Asymmetric bioreduction of β-ketoesters derivatives by Kluyveromyces marxianus: influence of molecular structure on the conversion and enantiomeric excess |
| title_short | Asymmetric bioreduction of β-ketoesters derivatives by Kluyveromyces marxianus: influence of molecular structure on the conversion and enantiomeric excess |
| title_sort | asymmetric bioreduction of β ketoesters derivatives by kluyveromyces marxianus influence of molecular structure on the conversion and enantiomeric excess |
| topic | biocatalysis β-ketoesters β-hydroxyesters HQSAR whole cell bioreduction |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652017005017104&lng=en&tlng=en |
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