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利用响应面法优化巴卡亭III生成10-DAB的工艺条件

发布时间:2019-01-21 17:59
【摘要】:10-脱乙酰基巴卡亭III(10-DAB)是紫杉烷类抗肿瘤药物多烯紫杉醇的前体物质。采用响应面法优化成团泛菌P2-A-8转化巴卡亭III生成10-DAB的工艺条件。利用Box-Behnken试验和方差分析,从菌体培养时间、菌体浓度OD600、底物终浓度、转化温度、转化时间5个方面优化成团泛菌P2-A-8转化巴卡亭III生成10-DAB的工艺条件。结果表明,获得最佳转化工艺条件为:菌体经过二级培养12 h,转接后调节初始OD600为3.0,此时,加入溶解于甲醇的巴卡亭III溶液,使其终浓度为0.007 mg/m L,32℃,200 r/min下转化4 d,此时10-DAB的生成率达到24.5%,比优化前提高了446.8%。实验结果表明,响应面法优化成团泛菌P2-A-8转化巴卡亭III生成10-DAB的工艺条件合理可行。该研究成果对于多烯紫杉醇生物合成具有重要的应用价值。
[Abstract]:III (10-DAB) is a precursor of docetaxel, a taxane antitumor drug. Response surface method (RSM) was used to optimize the process conditions for the transformation of Vaca III into 10-DAB by panbacterium P2-A-8. Box-Behnken test and variance analysis were used to optimize the process conditions for the transformation of III from P2-A-8 to 10-DAB from five aspects: cell culture time, final concentration of OD600, substrate, transformation temperature and transformation time. The results showed that the optimum transformation conditions were as follows: after 12 hours of secondary culture, the initial OD600 was adjusted to 3.0, and the final concentration of Vaca III dissolved in methanol was 0.007 mg/m L ~ (2 +) at 32 鈩,

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