title: [Asymmetric synthesis of atorvastatin intermediate by Pichia pastoris X-33].
abstract: Ethyl (R)-3-hydroxy-5-(1,3-dioxoisoindolin-2-yl)-pentanoate is a potential intermediate for the synthesis of HMG-CoA reductase inhibitor (atorvastatin) that can lower the cholesterol level in human blood. In this study, in order to synthesize ethyl (R)-3-hydroxy-5-(1,3-dioxoisoindolin-2-yl)-pentanoate by bioreduction, the yeast strains in our lab were screened. Ethyl (R)-3-hydroxy-5-(1,3-dioxoisoindolin-2-yl)-pentanoate was found to be produced efficiently from ethyl 5-(1,3-dioxoisoindolin-2-yl)-3-oxopentanoate by Pichia pastoris X-33. The effects of initial substrate concentration, reaction time, co-substrate, amount of yeast cells, pH, as well as the temperature on the yield and enantiomeric excesses (e.e. value) of product were examined in mono-phase system. The optimal reaction conditions are as fallows: substrate concentration 7 g/L, cell concentration 120 g/L, glucose concentration 120 g/L, pH 6.5, temperature 35 degrees C, reaction time 12 h, and the yield 93.12% with the high e.e. value of 98.55%.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science & Technology, Shanghai 200237, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhou
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Ren
authors.forename: Minjie
authors.initials: M
authors.lastname: Zhang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Sun
authors.forename: Dongzhi
authors.initials: D
authors.lastname: Wei
mesh_terms: D000924:Anticholesteremic Agents / Q000378:metabolism; D000069059:Atorvastatin; D002384:Catalysis; D004798:Enzymes / Q000378:metabolism; D005285:Fermentation; D006538:Heptanoic Acids / Q000378:metabolism; D054833:Isoindoles / Q000378:metabolism*; D010084:Oxidation-Reduction; D010421:Pentanoic Acids / Q000378:metabolism*; D010843:Pichia / Q000235:genetics / Q000378:metabolism*; D011758:Pyrroles / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D000924:Anticholesteremic Agents; D004798:Enzymes; D006538:Heptanoic Acids; D054833:Isoindoles; D010421:Pentanoic Acids; D011758:Pyrroles; C577247:ethyl (R)-3-hydroxy-5-(1,3-dioxoisoindolin-2-yl)-pentanoate; D000069059:Atorvastatin