Enantioselective synthesis of (S)-phenylephrine by whole cells of recombinant Escherichia coli expressing the amino alcohol dehydrogenase gene from Rhodococcus erythropolis BCRC 10909

摘要: Abstract (R)-phenylephrine [(R)-PE] is an α1-adrenergic receptor agonist that widely used in over-the-counter drugs to treat the common cold. We found Rhodococcus erythropolis BCRC 10909 can convert detectable level of 1-(3-hydroxyphenyl)-2-(methylamino) ethanone (HPMAE) (S)-PE by high performance liquid chromatography tandem mass spectrometry analysis. An amino alcohol dehydrogenase gene (RE_AADH) which possesses ability HPMAE was then isolated from R. and expressed Escherichia coli NovaBlue. The purified RE_AADH, tagged with 6×His, had a molecular approximately 30 kDa exhibited specific activity 0.19 μU/mg presence NADPH, indicating this enzyme could be categorized as NADP+-dependent short-chain reductase. E. NovaBlue cell expressing RE_AADH able more than 99% enantiomeric excess (ee), 78% yield productivity 3.9 mmol (S)-PE/L h 12 h at 30 °C pH 7. (S)-PE, recovered reaction mixture precipitation 11.3, converted (R)-PE (ee > 99%) Walden inversion reaction. This first reported biocatalytic process for production HPMAE.