烟曲霉酸的发酵培养基优化和反应器放大研究

Optimization of fermentation medium for helvolic acid production and reactor scale-up study

烟曲霉酸是一种四环三萜类结构的化合物,具有良好的抗菌活性和抗癌效果。该研究在单因素试验的基础上,对来源于海洋的烟曲霉菌(Aspergillus fumigatus)CY018发酵生产烟曲霉酸的培养基进行了优化及放大培养。结果表明,优化后发酵培养基为甘露醇39.88 g/L,硝酸钠2.25 g/L,牛肉膏3.54 g/L,丁二酸钠8.4 g/L,硫酸镁0.3 g/L,硫酸亚铁0.01 g/L,磷酸二氢钾0.67 g/L。初始pH值调至4.2,摇瓶装液量50 mL/250 mL,转速160 r/min,28℃培养9 d。在此优化培养基及发酵条件下,烟曲霉酸的产量达到68.49 mg/L,为优化之前的4.1倍。并在此基础上进行了5 L反应器的放大研究,在发酵第7天得到了烟曲霉酸的最大产量为54.81 mg/L。该实验为HA生产的放大制备与应用推广打下了基础。

Helvolic acid is a kind of tetracyclic triterpenoids, which shows effective antimicrobial activity and anticancer effect. On the basis of single factor experiment, the medium for marine derived Aspergillus furnigatus CY018 culture for helvolic acid production was optimized, and scale-up fermentation was studied. The optimal fermentation conditions were obtained as follows： marmitol 39.88 g/L, NaNO3 2.25 g/L, beef extract 3.54 g/L, Na2CzO4 8.4 g/L, MgSO4 0.3 g/L, FeSO4 0.01 g/L, KH2PO4 0.67 g/L. The optimal fermentation condition was initial pH 4.2, rotation liquid volume 50 ml/250 ml, shake speed 160 r/rain, temperature 28℃ for 9 d. Under the optimal condition, the yield of helvolic acid could achieve 68.49 mg/L, which was 4.1 times of the yield before optimization. The study of 5 L bio-reactor was conducted, and the maximum helvolic acid production of 54.81 mg/L was achieved in 7 d, which laid foundation for helvolic acid preparation and application.