Production of a Doubly Chiral Compound, (4 R ,6 R )-4-Hydroxy-2,2,6-Trimethylcyclohexanone, by Two-Step Enzymatic Asymmetric Reduction
| Autor: | Masaru Wada, Sakayu Shimizu, Michihiko Kataoka, Yumiko Noda, Hiroshi Takagi, Shigeru Nakamori, Ayumi Yoshizumi |
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| Rok vydání: | 2003 |
| Předmět: |
Double bond
Stereochemistry Glucose Dehydrogenases Stereoisomerism Saccharomyces cerevisiae Applied Microbiology and Biotechnology Cofactor Substrate Specificity Glucose dehydrogenase Escherichia coli Enantiomeric excess chemistry.chemical_classification Ecology biology Cyclohexanones Chemistry NADPH Dehydrogenase Glucose 1-Dehydrogenase Physiology and Biotechnology Biocatalysis biology.protein Stereoselectivity Chirality (chemistry) Food Science Biotechnology |
| Zdroj: | Applied and Environmental Microbiology. 69:933-937 |
| ISSN: | 1098-5336 0099-2240 |
| DOI: | 10.1128/aem.69.2.933-937.2003 |
| Popis: | A practical enzymatic synthesis of a doubly chiral key compound, (4 R ,6 R )-4-hydroxy-2,2,6-trimethylcyclohexanone, starting from the readily available 2,6,6-trimethyl-2-cyclohexen-1,4-dione is described. Chirality is first introduced at the C-6 position by a stereoselective enzymatic hydrogenation of the double bond using old yellow enzyme 2 of Saccharomyces cerevisiae , expressed in Escherichia coli , as a biocatalyst. Thereafter, the carbonyl group at the C-4 position is reduced selectively and stereospecifically by levodione reductase of Corynebacterium aquaticum M-13, expressed in E. coli , to the corresponding alcohol. Commercially available glucose dehydrogenase was also used for cofactor regeneration in both steps. Using this two-step enzymatic asymmetric reduction system, 9.5 mg of (4 R ,6 R )-4-hydroxy-2,2,6-trimethylcyclohexanone/ml was produced almost stoichiometrically, with 94% enantiomeric excess in the presence of glucose, NAD + , and glucose dehydrogenase. To our knowledge, this is the first report of the application of S. cerevisiae old yellow enzyme for the production of a useful compound. |
| Databáze: | OpenAIRE |
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