蒿属植物内生真菌Penicillium sp.抗癌活性产物的液体发酵工艺优化

Optimization of Fermentation Process of an Antitumor Metabolite Produced by Endophytic Fungus Penicillium sp.

编号为GZUCCZY0012的青霉属内生真菌Penicillium sp.代谢产物中的物质A疑似为青蒿素类化合物,体外抗癌实验表明物质A对人前列腺癌细胞PC3和人非小细胞肺癌细胞A549具有中等的细胞毒活力。本实验以物质A的含量为主要指标,通过单因素实验和正交实验的考察,并结合PB和中心组合设计,优化确定了适合物质A积累的GZUCCZY0012液体发酵培养基和培养条件。研究结果表明:GZUCCZY0012发酵生产物质A的最优培养基为麦芽糖47.52 g/L、NH4Cl 14.82 g/L、K2HPO41.5 g/L、MgSO42.0 g/L、KCl 2.0 g/L、ZnSO40.5 g/L、CaCl20.5g/L、FeSO40.5 g/L,pH 6.0,接种量4%(V/V),于26℃下摇瓶发酵14 d,物质A的产量可以达到(144.61±7.56)μg/mL,比优化前的含量(32.30±2.28)μg/mL提高了3.48倍。

The compound A extracted from a strain of endophytic fungi GZUCCZY0012 （Penicillium sp. ） was similar to the artemisinin, and showed cytotoxic toward the in vitro human tumor cell lines （lung A549 and prostate PC3 ）. The objective of the present work was to optimize the medium and the liquid fermentation condition of isolate GZUCCZY0012 for the production of compound A by single factor and orthogonal tests. The results showed that the best medium were as follows： maltose 47.52 g/L, NH4Cl 14.82 g/L, K2HPO4 1.5 g/L, MgSO4 2.0 g/L, KCl 2. 0 g/L, ZnSO4 0. 5 g/L, CaC12 0. 5 g/L, FeSO4 0.5 g/L, 6 of initial pH value, inoculation volume 4% （V/V） , 26 ℃, and 14 d of incubation period. The yield of this compound A could reach up to （ 144.61 ±7.56）μg/mL, which was 3.48 times as that from basic fermentation medium.