Asymmetric synthesis of tert-butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate using a self-sufficient biocatalyst based on carbonyl reductase and cofactor co-immobilization.
Bioprocess Biosyst Eng
; 43(1): 21-31, 2020 Jan.
Article
en En
| MEDLINE
| ID: mdl-31542820
tert-Butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate [(3R,5S)-CDHH] is the key chiral intermediate to synthesize the side chain of the lipid-lowering drug rosuvastatin. Carbonyl reductases showed excellent activity for the biosynthesis of (3R,5S)-CDHH. The requirement of cofactor NADH/NADPH leads to high cost for the industrial application of carbonyl reductases. In this study, a self-sufficient biocatalyst based on carbonyl reductase and NADP+ co-immobilization strategy was developed on an amino resin carrier LX-1000HAA (SCR-NADP+@LX-1000HAA). The self-sufficient biocatalyst achieved in situ cofactor regeneration and showed the activity recovery of 77.93% and the specific activity of 70.45 U/g. Asymmetric synthesis of (3R,5S)-CDHH using SCR-NADP+@LX-1000HAA showed high enantioselectivity (> 99% e.e.) and yield (98.54%). Batch reactions were performed for ten cycles without extra addition of NADP+, and the total yield of (3R,5S)-CDHH achieved at 10.56 g/g biocatalyst. The present work demonstrated the potential of the self-sufficient biocatalyst for the asymmetric biosynthesis of rosuvastatin intermediate.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Candida
/
Caproatos
/
Proteínas Fúngicas
/
Oxidorreductasas de Alcohol
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Enzimas Inmovilizadas
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Biocatálisis
/
NADP
Idioma:
En
Revista:
Bioprocess Biosyst Eng
Asunto de la revista:
BIOTECNOLOGIA
/
ENGENHARIA BIOMEDICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Alemania