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Biocatalytic preparation of a key intermediate of antifungal drugs using an alcohol dehydrogenase with high organic tolerance.
- Source :
-
Tetrahedron Letters: International Organ for the Rapid Publication of Preliminary Communications in Organic Chemistry . Nov2021, Vol. 84, pN.PAG-N.PAG. 1p. - Publication Year :
- 2021
-
Abstract
- [Display omitted] In this study, an alcohol dehydrogenase derived from Lactobacillus kefir (LkADH) was engineered and a simple and practical bioreduction system was developed for the preparation of (R)-2-chloro-1-(2, 4-dichlorophenyl) ethanol ((R)-CDPO), a key intermediate for the synthesis of antifungal drugs. Through active pocket iterative saturation mutagenesis, mutant LkADH-D18 (Y190C/V196L/M206H/D150H) was obtained with high stereoselectivity (99% ee, R vs 87% ee , S) and increased activity (0.44 µmol·min−1·mg−1). LkADH-D18 demonstrated NAD(P)H regeneration capability using a high concentration of isopropanol (IPA) as a co-substrate. Using 40% IPA (v/v), 400 mM of (R)-CDPO (90.1 g·L-1) was obtained via complete substrate conversion using 40 mg·mL−1 LkADH-D18 wet cells. The biocatalytic process catalyzed at constant pH with the cheap co-solvent IPA contributed to improved isolated yield of (R)-CDPO (97%), lower reaction cost, and simpler downstream purification, indicating the potential utility of LkADH-D18 in future industrial applications. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00404039
- Volume :
- 84
- Database :
- Academic Search Index
- Journal :
- Tetrahedron Letters: International Organ for the Rapid Publication of Preliminary Communications in Organic Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 153371034
- Full Text :
- https://doi.org/10.1016/j.tetlet.2021.153455