Soni Pankaj, Kansal Himani, Banerjee Uttam C
Department of Pharmaceutical Technology (Biotechnology), National Institute of Pharmaceutical Education and Research, SAS Nagar, India.
J Ind Microbiol Biotechnol. 2008 Mar;35(3):167-73. doi: 10.1007/s10295-007-0280-y. Epub 2007 Nov 28.
The effect of pH, aeration and mixing on the growth and production of carbonyl reductase by Candida viswanathii was investigated in a 6.6-l fermentor. Controlling the pH at 8.0 had a very significant effect on the enzyme production. Aeration and agitation influenced the dissolved oxygen concentration which in turn affected growth as well as enzyme production. A maximum carbonyl reductase activity (53 Umg(-1)) was attained in 24 h under the optimal cultivation conditions of controlled pH at 8.0, aeration rate 1 vvm and an agitation speed of 250 rpm at 25 degrees C. The enzyme activity was twice as high (56 Umg(-1)) in the fermentor as compared to a shake flask. Further, the duration of growth and enzyme production in the fermentor was shortened. Cells cultivated under the optimized conditions were used for the preparative scale reduction of N, N-dimethyl-(3-keto)-2-thienyl-propanamine to (S)-N, N-dimethyl-(3-hydroxy)-2-thienyl-propanamine, a key intermediate in the production of the important antidepressant drug (S)-duloxetine.
在6.6升发酵罐中研究了pH值、通气和搅拌对维斯瓦纳蒂念珠菌生长及羰基还原酶产生的影响。将pH值控制在8.0对酶的产生有非常显著的影响。通气和搅拌影响溶解氧浓度，进而影响生长和酶的产生。在25℃下，控制pH值为8.0、通气速率为1 vvm和搅拌速度为250 rpm的最佳培养条件下，24小时内羰基还原酶活性达到最大值（53 Umg(-1)）。与摇瓶相比，发酵罐中的酶活性高出两倍（56 Umg(-1)）。此外，发酵罐中生长和酶产生的持续时间缩短。在优化条件下培养的细胞用于将N，N-二甲基-（3-酮基）-2-噻吩基丙胺制备规模还原为（S）-N，N-二甲基-（3-羟基）-2-噻吩基丙胺，这是重要抗抑郁药（S）-度洛西汀生产中的关键中间体。
