Burkholderia cenocepacia: a new biocatalyst for efficient bioreduction of ezetimibe intermediate

Abstract

Ezetimibe is a selective acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitor used in hypercholesterolemia. Synthesis of ezetimibe requires enantiopure 3-[5-(4-fluorophenyl)-5(S)-hydroxypentanoyl]-4(S)-4-phenyl-1,3-oxazolidin-2-one (FOP alcohol) as a crucial intermediate which is produced by reduction of the corresponding prochiral ketone (FOP dione). A new biocatalyst from acclimatized soil was screened for bioreduction of the above prochiral ketone. The microorganism was identified by 16S mRNA sequencing, as Burkholderia cenocepacia. Various physicochemical conditions were optimized to increase cellmass and enzyme activity. The overall increase in cellmass concentration and enzyme activity was 2.06 and 1.85-fold, respectively. Various reaction conditions, for example pH, temperature, agitation, and cellmass concentration, were optimized for maximum product yield (chiral alcohol) with excellent enantioselectivity. Best reduction was achieved in phosphate buffer (50 mM, pH 8.0) at 40 degrees C (200 rpm) and the yield of enantiopure alcohol from the corresponding prochiral ketone was 54%. This biocatalyst was also used for the reduction of various other prochiral ketones.

Tween-20® Enhanced Bioreduction of Acetophenones Promoted by Daucus carota Root

“…Although the lack of reduction of 1h is contradictory to a previous report (12), these results are in line with other reports (13,14). It is well known that amino and hydroxyl groups play a significant role in the activity of the catalyst.…”

Enantiomer discrimination in β-phenylalanine degradation by a newly isolated Paraburkholderia strain BS115 and type strain PsJN

“…Further experiments with a different Paraburkholderia strain demonstrated that AP can be reduced by a carbonyl reductase (Singh et al 2009 ), which might serve as an evidence for further metabolization inside the cells. It is also known that Burkholderia sp.…”

Isolation and characterization of Burkholderia sp. strain CCA53 exhibiting ligninolytic potential

“…Two kinds of p -hydroxybenzoic acid esters, methyl paraben and propyl paraben, are degraded by B. latens (Amin et al 2010 ). Ezetimibe, a selective inhibitor of acyl-coenzyme A, was produced from reduction of 1-(4-fluorophenyl)-5-(2-oxo-4-phenyl-oxazolidin-3-yl)-pentane-1,5-dione in culture medium with B. cenocepacia (Singh et al 2009 ). It was thus anticipated that Burkholderia sp.…”