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

Autor:	Oliveira SSS; Faculdade de Farmácia, Universidade Federal Fluminense/UFF, Rua Mário Viana, 523, Santa Rosa, 24241-000 Niterói, RJ, Brazil., Bello ML; Faculdade de Farmácia, Universidade Federal do Rio de Janeiro/UFRJ, Centro de Ciências da Saúde, Av. Carlos Chagas Filho, 373, Cidade Universitária, 21941-599 Rio de Janeiro, RJ, Brazil., Rodrigues CR; Faculdade de Farmácia, Universidade Federal do Rio de Janeiro/UFRJ, Centro de Ciências da Saúde, Av. Carlos Chagas Filho, 373, Cidade Universitária, 21941-599 Rio de Janeiro, RJ, Brazil., Azevedo PL; Instituto de Química, Universidade Federal do Rio de Janeiro/UFRJ, Centro de Tecnologia, Av. Athos da Silveira Ramos, 149, Bloco A, Cidade Universitária, 21941-909 Rio de Janeiro, RJ, Brazil., Ramos MCKV; Instituto de Química, Universidade Federal do Rio de Janeiro/UFRJ, Centro de Tecnologia, Av. Athos da Silveira Ramos, 149, Bloco A, Cidade Universitária, 21941-909 Rio de Janeiro, RJ, Brazil., Aquino-Neto FR; Instituto de Química, Universidade Federal do Rio de Janeiro/UFRJ, Centro de Tecnologia, Av. Athos da Silveira Ramos, 149, Bloco A, Cidade Universitária, 21941-909 Rio de Janeiro, RJ, Brazil., Fiaux SB; Faculdade de Farmácia, Universidade Federal Fluminense/UFF, Rua Mário Viana, 523, Santa Rosa, 24241-000 Niterói, RJ, Brazil., Dias LRS; Faculdade de Farmácia, Universidade Federal Fluminense/UFF, Rua Mário Viana, 523, Santa Rosa, 24241-000 Niterói, RJ, Brazil.
Jazyk:	angličtina
Zdroj:	Anais da Academia Brasileira de Ciencias [An Acad Bras Cienc] 2017 Jul-Sep; Vol. 89 (3), pp. 1403-1415. Date of Electronic Publication: 2017 Aug 07.
DOI:	10.1590/0001-3765201720170118
Abstrakt:	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.
Databáze:	MEDLINE
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