Journal
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
Volume 84, Issue 3, Pages 397-405Publisher
SPRINGER
DOI: 10.1007/s00253-009-2105-6
Keywords
(S)-4-Bromo-3-hydroxybutyrate; Intermediate for statin compounds; Enzymatic production; Aldo-keto reductase; Penicillium citrinum; Alcohol dehydrogenase; Leifsonia sp.
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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.
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