• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biotechnology and Bioengineering >Scale-up and intensification of (S)-1-(2-chlorophenyl)ethanol bioproduction: Economic evaluation of whole cell-catalyzed reduction of o-Chloroacetophenone
【24h】

Scale-up and intensification of (S)-1-(2-chlorophenyl)ethanol bioproduction: Economic evaluation of whole cell-catalyzed reduction of o-Chloroacetophenone

机译：（S）-1-（2-氯苯基）乙醇生物生产的规模化和集约化：全细胞催化还原邻氯苯乙酮的经济评价

获取原文
获取原文并翻译 | 示例
       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Escherichia coli cells co-expressing genes coding for Candida tenuis xylose reductase and Candida boidinii formate dehydrogenase were used for the bioreduction of o-chloroacetophenone with in situ coenzyme recycling. The product, (S)-1-(2-chlorophenyl)ethanol, is a key chiral intermediate in the synthesis of polo-like kinase 1 inhibitors, a new class of chemotherapeutic drugs. Production of the alcohol in multi-gram scale requires intensification and scale-up of the biocatalyst production, biotransformation, and downstream processing. Cell cultivation in a 6.9-L bioreactor led to a more than tenfold increase in cell concentration compared to shaken flask cultivation. The resultant cells were used in conversions of 300mM substrate to (S)-1-(2-chlorophenyl)ethanol (e.e. >99.9%) in high yield (96%). Results obtained in a reaction volume of 500mL were identical to biotransformations carried out in 1mL (analytical) and 15mL (preparative) scale. Optimization of product isolation based on hexane extraction yielded 86% isolated product. Biotransformation and extraction were accomplished in a stirred tank reactor equipped with pH and temperature control. The developed process lowered production costs by 80% and enabled (S)-1-(2-chlorophenyl)ethanol production within previously defined economic boundaries. A simple and efficient way to synthesize (S)-1-(2-chlorophenyl)ethanol in an isolated amount of 20g product per reaction batch was demonstrated.
机译：大肠杆菌细胞共表达编码假丝酵母木糖还原酶和博伊丁氏假丝酵母甲酸脱氢酶的基因用于邻氯苯乙酮的生物还原和原位辅酶回收。 （S）-1-（2-氯苯基）乙醇产物是合成新型polo-like激酶1抑制剂的关键手性中间体。以克为单位的酒精生产需要加强和扩大生物催化剂的生产，生物转化和下游加工。与摇瓶培养相比，在6.9 L生物反应器中进行细胞培养可使细胞浓度增加十倍以上。所得的细胞以高产率（96％）用于300mM底物到（S）-1-（2-氯苯基）乙醇（例如＞ 99.9％）的转化中。在500mL反应体积中获得的结果与1mL（分析性）和15mL（制备性）规模的生物转化相同。基于己烷萃取的产物分离优化产生86％的分离产物。生物转化和提取是在配有pH和温度控制装置的搅拌釜反应器中完成的。所开发的方法将生产成本降低了80％，并在先前定义的经济范围内实现了（S）-1-（2-氯苯基）乙醇的生产。演示了一种简单有效的方法，以每反应批次20g的分离量合成（S）-1-（2-氯苯基）乙醇。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号