Asymmetric bioreduction of beta-ketoesters derivatives by Kluyveromyces marxianus: influence of molecular structure on the conversion and enantiomeric excess

作者：Oliveira Simone S S; Bello Murilo L; Rodrigues Carlos R; De Azevedo Paula L; Ramos Maria C K V; De Aquino Neto Francisco R; Fiaux Sorele B; Dias Luiza R S^*

来源：ANAIS DA ACADEMIA BRASILEIRA DE CIENCIAS, 2017, 89(3): 1403-1415.

DOI：10.1590/0001-3765201720170118

• biocatalysis
• beta-ketoesters
• beta-hydroxyesters
• HQSAR
• whole cell bioreduction

This study presents the bioreduction of six beta-ketoesters by whole cells of Kluyveromyces marxianus and molecular investigation of a series of 13 beta-ketoesters by hologram quantitative structure-activity relationship (HQSAR) in order to relate with conversion and enantiomeric excess of beta-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 beta-ketoesters series LUMO maps showed that the beta-carbon of the ketoester scaffold are exposed to undergo nucleophilic attack, suggesting a more favorable beta-carbon side to enzymatic reduction based on adopted molecular conformation at the reaction moment. The HQSAR method was performed on the beta-ketoesters derivatives separating them into those provided predominantly (R)-or (S)-beta-hydroxyesters. The HQSAR models for both (R)-and (S)-configuration showed high predictive capacity. The HQSAR contribution maps suggest the importance of beta-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 beta-carbon side to the bioconversion to (S)-and (R)-enantiomers.

• 出版日期2017-9