Paper
Biocatalytic production of (S)-4-bromo-3-hydroxybutyrate and structurally related chemicals and their applications
Published Jul 11, 2009 · Hiroyuki Asako, M. Shimizu, N. Itoh
Applied Microbiology and Biotechnology
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Abstract
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 β-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.
This study developed a novel biotechnological process for producing (S)-4-bromo-3-hydroxybutyrate using E. coli transformants, suitable for industrial production of statin intermediates.
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