Asymmetric synthesis of atorvastatin intermediate by Pichia pastoris X-33.
- Author:
Jianping ZHOU
1
;
Yuhong REN
;
Minjie ZHANG
;
Xiaofeng SUN
;
Dongzhi WEI
Author Information
1. State Key Laboratory of Bioreactor Engineering, East China University of Science & Technology, Shanghai 200237, China.
- Publication Type:Journal Article
- MeSH:
Anticholesteremic Agents;
metabolism;
Atorvastatin Calcium;
Catalysis;
Enzymes;
metabolism;
Fermentation;
Heptanoic Acids;
metabolism;
Isoindoles;
metabolism;
Oxidation-Reduction;
Pentanoic Acids;
metabolism;
Pichia;
genetics;
metabolism;
Pyrroles;
metabolism;
Stereoisomerism
- From:
Chinese Journal of Biotechnology
2011;27(4):579-583
- CountryChina
- Language:Chinese
-
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%.
