Biocatalytic production of (S)-4-bromo-3-hydroxybutyrate and structurally related chemicals and their applications.
The enzymatic production of (S)-4-bromo-3-hydroxybutyrate has been poorly studied compared with (S)-4-chloro-3-hydroxybutyrate. This can be attributed to the toxicity of bromide for biocatalysis. Recently, we isolated cDNA that encodes Penicillium citrinum beta-keto ester reductase (KER) and the gene that encodes Leifsonia sp. alcohol dehydrogenase, which catalyzes the reduction of methyl 4-bromo-3-oxobutyrate to methyl (S)-4-bromo-3-hydroxybutyrate with high optical purity and productivity and expressed them in Escherichia coli. Moreover, protein engineering was performed using error-prone PCR-based random mutagenesis to improve the thermostability and enantioselectivity of KER. This review focuses on the establishment of a novel biotechnological process for the production of (S)-4-bromo-3-hydroxybutyrate using E. coli transformants. This process is suitable for industrial production of (S)-4-bromo-3-hydroxybutyrate, an intermediate for statin compounds.
Asako
Hiroyuki
H
Organic Synthesis Research Laboratory, Sumitomo Chemical Co., Ltd., 1-98, Kasugade-naka 3-chome, Konohana-ku, Osaka, 554-8558, Japan. asako@sc.sumitomo-chem.co.jp
Shimizu
Masatoshi
M
Itoh
Nobuya
N
D000192:Actinomycetales / Q000201:enzymology / Q000235:genetics; D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D055162:Biocatalysis; D001709:Biotechnology / Q000379:methods*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics*; D006885:Hydroxybutyrates / Q000737:chemistry / Q000378:metabolism*; D010407:Penicillium / Q000201:enzymology / Q000235:genetics; D015202:Protein Engineering / Q000379:methods
D006885:Hydroxybutyrates; C496653:methyl-4-bromo-3-hydroxybutyrate; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000426:Alcohol Dehydrogenase; D000449:Aldehyde Reductase