Asymmetric Bioreduction of a β-Tetralone to Its Corresponding (S)-Alcohol by the Yeast Trichosporon capitatum NY 1890

概要

論文の詳細を見る
The yeast Trichosporon capitatum MY 1890 was identified by microbial screening as a suitable biocatalyst for the asymmetric bioreduction of 6-bromo-β-tetralone to its corresponding (S)-alcohol (β-tetraol). This β-tetralol is a precursor to the chiral drug candidate MK-0499,a potassium channel blocker targeted for the treatment of ventricular arrhythmias. Process development studies, employing statistical exploratory designs, yielded a 10-fold increase in the rate of bioreduction and improved the (S)-β-tetraol enantiometric excess from 71% to 99%. The (S)-β-tetralol enantiometric excess was found to be highly dependent on glucose catabolism by T. capitatum. Elevated enantiomeric excesses were achieved when switching to a glycerol containing medium. Other process parameters such as pH, temperature and medium composition were found to mostly influence the rate of bioreduction. The developed shake flask process was scaled up to laboratory reactors (23-l scale) and supported the production of gram quantities of highly optically pure (S)-β-tetralol.
社団法人日本生物工学会の論文
1996-04-25