黄河三角洲土曲霉Aspergillus terreus OUCMDZ-1925中具抗菌活性的聚酮类天然产物

The antibacterial polyketides of Aspergillus terreus OUCMDZ- 1925 from Yellow River delta

作者利用化学与生物活性相集成的筛选方法,从采自黄河三角洲地区——东营黄河口的梭鱼Chelon haematocheilus的内脏中分离鉴定了1株耐盐真菌土曲霉Aspergillus terreus OUCMDZ-1925,其发酵产物具有抗枯草芽孢杆菌活性。进一步采用色谱分离、波谱鉴定,从其固体发酵(大米培养基)中分离鉴定了5个化合物,即右旋丁内酯I(1)、丁内酯IV(2)、丁内酯II(3)、丁内酯III(4)和3,5,6-三甲基-2,4-二羟基苯甲酸甲酯(5)。并发现化合物1–3和5对金黄色葡萄球菌(ATCC51650)有强的抑菌活性(最小抑菌浓度均为0.31μg/mL,阳性对照环丙沙星的最小抑菌浓度为0.16μg/mL),化合物1和2对产气杆菌(ATCC13408)以及化合物1和3对枯草芽孢杆菌(ATCC93151)有中等的抑菌活性(最小抑菌浓度分别为6.25μg/mL和12.50μg/mL,阳性对照环丙沙星的最小抑菌浓度分别为1.25μg/mL和5.0μg/mL),化合物1–5对大肠杆菌(ATCC25922)以及化合物4对金黄色葡萄球菌(ATCC51650)有弱的抑制活性,且化合物1的产量高,达2.5g/kg,为其后续研究提供了新的药源。

The Yellow River delta formed from the convergence of the Yellow River mouth and the Bohai Sea possesses a unique wetland environment different from both the sea and the land. This special ecosystem is rich in salt-and alkali-tolerant microorganisms. By means of an integrated chemical and antibacterial screening method, a salt-tolerant fungal strain,Aspergillus terreus OUCMDZ-1925 was isolated and identified from the internal organs of Chelon haematocheilus from the Yellow River estuary, Dongying, Shandong, China. The metabolites ofA. terreus OUCMDZ-1925 in solid state fermentation （rice medium） showed antibacterial effects on Bacillus subtilis. Chemical investigation resulted in the isolation and identification of （＋）-butyrolactone I （1） with high yield （2.5g/kg）, along with the other four minor polyketides, butyrolactone IV （2）, butyrolactone Ⅱ （3）, butyrolactone Ⅲ （4） and methyl 2,4-dihydroxy-3,5,6-trimethylbenzoate （5）. Compounds 1-3 and 5 showed strong antibacterial effects on Staphylococcus aureus （ATCC 51650） with MIC values of 0.31μg/mL （positive control, ciprofloxacin, MIC 0.16μg/mL）. The moderate antibacterial activities were first observed for compounds 1 and 2 against Enterobacter aerogenes （ATCC 13408）, and for compounds 1 and 3 against Bacillus subtilis （ATCC 93151） with MIC values of 6.25μg/mL and 12.50μg/mL, respectively （positive control, ciprofloxacin, MIC 1.25μg/mL and 5.0μg/mL, respectively）. In addition, compounds 1-5 and 4 displayed weak antibacterial effects on Escherichia coli （ATCC 25922） and S. aureus （ATCC 51650）, respectively.