摘要
目的对海洋来源真菌Aspergillus terreus中的(+)-terrein代谢产物进行发酵优化,以期获得足够的样品进行药理活性评价。方法采用不同发酵条件对微生物进行发酵优化,运用柱色谱层析技术对目标产物进行分离纯化,对化合物进行细胞毒及抗细菌活性评价。结果研究表明,最优发酵条件为土豆液体发酵培养基,发酵时间为28d,在该条件下目标产物单一,易分离纯化。用上述最优发酵条件,摇床发酵时间12d的产量与静置发酵28d的产量相当。细胞毒活性测试结果显示,(+)-terrein具有强的细胞毒活性,对NCIH460、A549和BT474肿瘤细胞株的IC50值分别为3.12、3.32和3.45μg/mL。结论在优化条件下,静置发酵28d,(+)-terrein的产量可达0.254g·L-1,而摇床发酵12d其产量为0.263g·L^(-1),明显缩短了发酵时间。此外,该化合物对NCI-H460、A549和BT474肿瘤细胞具有较好的细胞毒活性,具有开发为抗癌药物的潜在价值。
Objective To increase the yield of (+)- terrein by optimizing the fermentation conditions for the marine-derived fungus Aspergillus terreus (RA2905) and evaluate the pharmaceutical activities of terrein. Methods Different fermentation mediums were designed to investigate the optimum fermenta- tion condition. The organic extract of the fungus was separated and purified by column chromatography methods. Cytotoxic activity and antibacterial activity of compound (+)- terrein were also evaluated. Results The optimum fermentation condition was PDA broth with stable fermentation time of 4 weeks. Under the fermentation of PDA broth, marine- derived fungus A. terreus produced a single target prod- uct (+)- terrein, which was easily to be purified. Fermentation time could be shorten to 12 days using the above optimized PDA broth with shaking, which had similar yields. Cytotoxic results indicated that (q-)- terrein showed potent cytotoxic activities against NCI- H460, A549 and BT474, with ICs0 values of 3. 12,3.32 and 3. 45 μg/mL, respectively. Conclusion The yield of (+)- terrein was improved to 0. 254 g · g-1 under the optimized fermentation conditions. Fermentation time could be shorten to 12 days under flask- shaking fermentation with the same culture medium. And the production yield was 0. 263 g · L-1 which was equivalent to that of stable fermentation. (+- Terrein showed strong cyto- toxic activity to NCI- H460, A549 and BT474 with the potential to be developed into antitumor agent.
作者
吴洪娥
牟晓凤
房耀维
邵长伦
WU Hong-e MOU Xiao-feng FANG Yao-wei SHAO Chang-lun(Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy,Ocean University of China, Qingdao 266003, China Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266200, China)
出处
《中国海洋药物》
CAS
CSCD
2017年第4期25-28,共4页
Chinese Journal of Marine Drugs
基金
国家自然科学基金项目(41322037)
山东省自然科学基金项目(JQ201510)
国家海洋局海洋公益性行业科研专项(201405038)资助