초록
Diketoreductase from Acinetobacter baylyi ATCC 33305 is a unique carbonyl reductase, which can stereoselectively reduce ethyl-6-(benzyloxy)-3,5-dioxohexanoate to ethyl 3R,5S-6-(benzyloxy)-3,5-dihydroxy-hexanoate, an advanced intermediate for statin drugs. In the present study, we explored an aqueous-organic biphasic reaction system to make this biocatalyst more practical and valuable. Different from most oxidoreductases, diketoreductase displayed an excellent tolerance to certain organic solvents without any changes on the catalytic properties. After optimizing reaction conditions, an aqueous-hexane (1:1) biphasic system was established for the preparation of 3R,5S-dihydroxy product by diketoreductase. This system was further scaled up to 0.5l at a substrate concentration of 105g/l (378mM), and the 3R,5S-hydroxy product was obtained with a yield of 83.5% and excellent stereoselectivity (de>99.5%, ee>99.5%).