Process Development for the Production of (R)-(鈭?-Mandelic Acid by Recombinant Escherichia coli Cells Harboring Nitrilase from Burkholderia cenocepacia J2315
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- 作者：Hualei Wang ; Haiyang Fan ; Huihui Sun ; Li Zhao ; Dongzhi Wei
- 刊名：Organic Process Research & Development
- 出版年：2015
- 出版时间：December 18, 2015
- 年：2015
- 卷：19
- 期：12
- 页码：2012-2016
- 全文大小：248K
- ISSN：1520-586X
文摘
(R)-(鈭?-Mandelic acid is an important chiral building block that is widely used in pharmacy and the production of fine chemicals. A more advanced method for obtaining (R)-(鈭?-mandelic acid is direct hydrolysis of the corresponding racemic mandelonitrile. In order to develop a cost-effective process, a highly efficient enantioselective nitrilase BCJ2315 from Burkholderia cenocepacia J2315 was used for the biotransformation of mandelonitrile to (R)-(鈭?-mandelic acid. The recombinant Escherichia coli M15/BCJ2315 showed high substrate tolerance and could completely hydrolyze up to 250 mM of mandelonitrile. A fed-batch reaction was performed by periodically or continuously dosing the substrate into the reactor to alleviate substrate inhibition in a monophasic buffer system. Finally, the highest substrate loading (2.9 M) was achieved in the continuous fed batch reaction mode, giving (R)-(鈭?-mandelic acid at the highest concentration (2.3 M, 350 g/L) with 97.4% ee ever reported. The hydrolysis process was easily scaled up to 2 and 10 L, indicating the potential for the industrial production of optically pure (R)-(鈭?-mandelic acid.