1. Field of the Invention
The present invention relates to a method for producing ester of (S)-.gamma.-halogenated-.beta.-hydroxybutyric acid. In particular, the present invention relates to an efficient method for producing ester of (S)-.gamma.-halogenated-.beta.-hydroxybutyric acid having a high optical purity, based on the use of a microorganism belonging to a specified genus or a taxonomic unit.
2. Description of the Related Art
Optically active ester of .gamma.-halogenated-.beta.-hydroxybutyric acid is useful as a raw material for synthesizing optically active compounds or synthetic intermediates thereof, to be utilized for various pharmaceuticals and agricultural chemicals. For example, the optically active ester of .gamma.-halogenated-.beta.-hydroxybutyric acid can be converted into side chain moieties of optically active hydroxy acid derivatives which are common to various HMG-CoA reductase inhibitors (therapeutic agents for hyperlipemia) such as compactin and pravastatin. In order to produce the optically active ester of .gamma.-halogenated-.beta.-hydroxybutyric acid, investigations have been hitherto made to utilize microbial abilities to effect asymmetric reduction. There have been a large number of reports on the production of optically active ester of .gamma.-halogenated-.beta.-hydroxybutyric acid based on such a microbial process.
These, for example, methods include: (1) a method based on the use of microbial cells of a yeast belonging to, for example, the genus Candida, Debaryomyces, Saccharomyces, Pichia, or Hansenula (Japanese Patent Publication No. 4-7195); (2) a method based on the use of a culture liquid or separated microbial cells of a mold belonging to, for example, the genus Stemphylium, Alternaria, Corynespora, or Preussia (Japanese Laid-Open Patent Publication No. 6-38776); (3) a method based on the use of microbial cells of a bacterium belonging to, for example, the genus Brevibacterium, Escherichia, or Lactobacillus, or a yeast belonging to, for example, the genus Kluyveromyces, Saccharomycopsis, or Stephanoascus (Japanese Laid-Open Patent Publication No. 6-209782); and (4) a method based on the use of an enzyme of a yeast or a mold belonging to, for example, the genus Rhodotorula, Fusarium, Paecilomyces, or Verticillium to make a reaction in a two-phase system of water-organic solvent (Japanese Laid-Open Patent Publication No. 63-309195).
However, in any of the production methods described above, there is a limitation on the type of microorganisms which can be used. Certain microogranisms cannot be used since they involve problems in that (1) the reaction velocity is small, and it takes a long time to perform the reaction, (2) the concentration of an accumulated product cannot be increased, and (3) only a product having a low optical purity can be obtained. In view of such circumstances, there is a need to establish a production method which is excellent ecconomically and which makes it possible to produce optically active ester of .gamma.-halogenated-.beta.-hydroxybutyric acid having a high optical purity, at a highly accumulated concentration and at a high yield.