(R)-α-羟基苯乙酸是重要的药物合成中间体,本文研究Bacillus sp.HB20在含离子液体([bmim]Cl)体系中催化合成(R)-α-羟基苯乙酸。首先采用Plackett-Burman试验设计法筛选出3个主要因素:离子液体浓度、反应温度、底物浓度。然后用最陡爬坡方法逼近最大响应区域,再用Box-Behnken试验设计和响应面分析法进行回归分析,确定出3个主要影响因素的最佳生产条件为:离子液体含量34.3g/L、反应温度33℃、底物浓度15.3mmol/L。得到的最大生产产率为82.39%,比优化前提高了21.66%。结果表明采用响应面方法有效地提高了(R)-α-羟基苯乙酸的产率,为手性药物的工业化生产提供了1条新的绿色途径。
(R)-α-Hydroxyphenylacetic acid ((R)-HPA) was an important drug intermediates. In the current study, Bacillus sp.HB20 was used to catalyze the reduction of phenylglyoxylic acid (PGA) to (R)-HPA in the system containing ionic liquid ([bmim]Cl) and response surface methodology was successfully used to optimize the production of (R)-HPA. A significant influence of ionic liquid (IL) content, reaction temperature, and PGA concentration on (R)-HPA production was noted with Plackett-Burman design and the steepest ascent was applied to approach the optimal response area. Then, a three-level Box-Behnken design was employed to optimize the culture conditions for the production of (R)-HPA. The optimal conditions to achieve the optimal (R)-HPA production were determined: IL content, 34.3 g/L; reaction temperature, 33 ℃; PGA concentration, 15.3 mmol/L. The maximum production of (R)-HPA was 82.39 %, which was about 21.66 % increase compared with that obtained from the original culture conditions. It can be concluded that using response surface methodology to improve the (R)-HPA yield is available. It provides a new green method for the industrial production of chiral drugs.