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-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.

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“…K. marxianus is also distinguished by thermotolerance (Lane et al, 2011 ), and the fastest reported growth rate of any eukaryote (Groeneveld et al, 2009 ). Recent years have seen increasing interest in new applications such as production of biomolecules (Hughes et al, 2017 ; Lin et al, 2017 ), biocatalysis (Oliveira et al, 2017 ; Wang et al, 2017 ) and heterologous protein production (Gombert et al, 2016 ; Lee et al, 2017 ).…”

Potential of Thermotolerant Ethanologenic Yeasts Isolated from ASEAN Countries and Their Application in High- Temperature Fermentation

“…marxianus is also distinguished by its thermotolerance [36,87] and the highest growth rate in eukaryotes [88]. In recent years, interest also increased in several new applications such as production of biomolecules [89,90], biocatalysts [91,92], and heterologous protein expression [93,94].…”