Biocompatible ionic liquids act as a substrate reservoir and an in situ extracting agent in biotransformations with whole cells (see scheme). In the reduction of 4‐chloroacetophenone to (R)‐1‐(4‐chlorophenyl)ethanol, high product concentration (82 g L−1) and purity (99.6 % ee) were achieved without the addition of cofactors and without damaging the biocatalyst.
An efficient fedbatch process for the production of Lactobacillus kefir DSM 20587 cells was developed. An improvement in space time yield of 270% (3.7 g(DCW) l(-1)-day(-1)) and in final enzyme activity of 440% (9.1 U/ml) was achieved on a 150 l scale by controlling the oxygen transfer rate to 7--9 mmol l(-1) h(-1). The cells exhibited good and highly stereoselective reducing activities against tert-butyl 6-chloro-3,5-dioxohexanoate. tert-Butyl (3R,5S)-6-chloro-dihydroxyhexanoate, a chiral building block for HMG-CoA reductase inhibitor synthesis, was produced with 47.5% yield and >99% ee at C(3)3 and C(5)5 in a simple batch biotransformation process.
An efficient whole cell biotransformation process using Lactobacillus kefir was developed for the asymmetric synthesis of tert-butyl (3R, 5S) 6-chloro-dihydroxyhexanoate, a chiral building block for the HMG-CoA reductase inhibitor. The effects of buffer concentration, temperature, pH and oxygen on the asymmetric reduction were investigated in batch reactions. Improvements in final product concentration and yields of 153% (120 mM) and 79% (0.85 mol/mol) with respect to the batch-process were achieved in an optimised fed-batch process. The pure substrate tert-butyl-6-chloro-3,5-dioxohexanoate was dispersed as microdroplets into the reaction system. This resulted in a space-time yield of 4.7 mmol l(-1) h(-1). A diastereomeric excess of >99% was measured for (3R, 5S) and (3S, 5S) tert-butyl 6-chloro-dihydroxyhexanoate.
Als biokompatibles Substratreservoir und In‐situ‐Extraktionsmittel fungiert die ionische Flüssigkeit bei Ganzzell‐Biotransformationen im Zweiphasensystem Puffer/ionische Flüssigkeit. Am Beispiel der Reduktion von 4‐Chloracetophenon zu (R)‐1‐(4‐Chlorphenyl)ethanol (siehe Schema) wird belegt, dass mit einer solchen Prozessführung ohne Zusatz teurer Cofaktoren hohe Produktkonzentrationen (82 g L−1) und ‐reinheiten (99.6 % ee) erzielt werden können.
klusiver der erforderlichen Instrumentierung und einer strukturangepassten Steuerung zur optimalen Produktbildung (s. Abb.).
Abbildung.Ansicht des Enzym-Membran-Reaktors.
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