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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28 d,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28 d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NCI-H460、A549和BT474肿瘤细胞株的IC50值分别为3.12、3.32和3.45 μg/mL.结论 在优化条件下,静置发酵28 d,(+)-terrein的产量可达0.254 g·L-1,而摇床发酵12 d其产量为0.263 g·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 fermentation 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 product (+)-terrein,which was easily to be purified.Fermentation time could be shorten to 12 days usingthe above optimized PDA broth with shaking,which had similar yields.Cytotoxic results indicated that (+)-terrein showed potent cytotoxic activities against NCI-H460,A549 and BT474,with IC50 values of 3.12,3.32 and 3.45 μ g/mL,respectively.Conclusion The yield of (+)-terrein was improved to 0.254 g · L-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 cytotoxic activity to NCI-H460,A549 and BT474 with the potential to be developed into antitumor agent.