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Optimization Strategies for Purification of Mycophenolic Acid Produced by Penicillium brevicompactum.
Applied Biochemistry and Biotechnology ( IF 3.1 ) Pub Date : 2020-01-06 , DOI: 10.1007/s12010-019-03204-w
Shubhankar Anand 1 , Pradeep Srivastava 1
Affiliation  

The microbial fermentation of Penicillium brevicompactum produces secondary metabolite mycophenolic acid (MPA), which exhibits antifungal, antiviral, antibacterial, and antitumor activity. It is also a potent, selective, non-competitive, and reversible inhibitor of the human inosine monophosphate dehydrogenase (IMPDH). This study is an attempt to optimize the MPA production through a fermentation process using Penicillium brevicompactum and its further purification process optimization. In the batch fermentation process, the maximum concentration of MPA (1.84 g/L) was attained in a 3.7 L stirred tank reactor. Response surface methodology (RSM) using central composite design (CCD) was employed as a statistical tool to investigate the effect of pH, the volume of eluent and flow rate of the mobile phase on MPA purification process. Under optimum conditions, the experimental yield was observed to be 84.12%, which matched well with the predictive yield of 84.42%. High-performance liquid chromatography (HPLC) and Fourier-transform infrared spectroscopy (FTIR) analysis of the fermented product was carried out to confirm the presence of mycophenolic acid. The MPA purification was done by using column chromatography technique. The purification of broth involved mycophenolic acid extraction by selecting different solvents on the basis of polarity and the extraction efficiency of solvent. Various solid support materials were used for MPA purification in column chromatography. The MPA recovery through alumina column was observed to be 84.12% under the optimum conditions, which was maximum elution as compared with other support materials. The optimized purification process yielded pure MPA crystals.



中文翻译:

短小青霉产生的麦考酚酸纯化的优化策略。

短小青霉菌的微生物发酵产生次级代谢产物麦考酚酸(MPA),其具有抗真菌,抗病毒,抗菌和抗肿瘤活性。它也是人肌苷单磷酸脱氢酶(IMPDH)的有效,选择性,非竞争性和可逆抑制剂。这项研究是通过使用短青霉菌发酵工艺优化MPA产量的尝试。及其进一步纯化工艺的优化。在分批发酵过程中,在3.7 L搅拌釜反应器中达到了MPA的最大浓度(1.84 g / L)。采用中心复合设计(CCD)的响应表面方法(RSM)作为统计工具,以研究pH,洗脱液体积和流动相流速对MPA纯化过程的影响。在最佳条件下,观察到实验产率为84.12%,与预测产率84.42%非常吻合。对发酵产物进行了高效液相色谱(HPLC)和傅里叶变换红外光谱(FTIR)分析,以确认麦考酚酸的存在。通过使用柱色谱技术进行MPA纯化。肉汤的纯化涉及通过根据极性和溶剂的提取效率选择不同的溶剂来提取麦考酚酸。各种固体载体材料用于柱色谱法中的MPA纯化。在最佳条件下,通过氧化铝柱的MPA回收率为84.12%,与其他载体材料相比,这是最大的洗脱。优化的纯化过程可产生纯MPA晶体。

更新日期:2020-01-06
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