中文摘要：

目的研究碱胁迫对放线菌次生代谢产物的影响，寻找结构新颖并具有抗菌和肿瘤细胞毒活性的化合物。方法采用化学和生物活性相结合的集成筛选方法，从耐碱放线菌中筛选获得代谢产物丰富并具有生物活性的目标菌株；通过碱胁迫目标菌株，利用硅胶柱色谱、凝胶柱色谱和高效液相色谱等方法对发酵产物进行分离和纯化，运用波谱学和钼靶X-射线单晶衍射分析方法鉴定化合物的结构。结果筛选到一株高产吩嗪生物碱的耐碱放线菌OUCMDZ-1368，鉴定为链霉菌Streptomyces sindenensis；该菌株在pH9的培养基中的次生代谢产物的产量最大，从其发酵产物中分离鉴定了11个化合物，其结构分别为phenazine-1-carboxamide（1，主产物）、phenazine-1-carboxylic acid（2，主产物）、（E）-2-non-1-en-1-yl-4（1H）quinolone（3）、2-methyl-4（1H）quinolone（4）、2-heptyl-4（1H）quinolone（5）、2-nonyl-4（1H）quinolone（6）、2-undecyl-4（1H）quinolone（7）、2-heptyl-3-hydroxy-4（1H）quinolone（8）、2-nonyl-3-hydroxyl-4（1H）quinolone（9）、S-methyl-2，4-dihydroxy-3，5-dimethyl-6-isopropylbenzothioate（10）和N-[2-（4-hydroxyphenyl）ethyl]acetamide（11）；化合物1和2对A549细胞有中等程度抑制活性，IC50分别为4．9和5．0μmol／L，化合物1—10分别对金黄色葡萄球菌、枯草杆菌、铜绿假单孢菌、产气杆菌以及白念珠菌表现出不同程度的抑制作用（MIC17～45μmol／L）。结论培养基的pH值影响放线菌的次生代谢产物，通过碱调节可以诱导微生物产生不同的活性代谢产物。

英文摘要：

Objective To study the effect of alkaline stress on the secondary metabolites of actinomycete, and to identify compounds with antibacterial and cytotoxic activities. Methods Using a screening method integrated chemical property and biological activity to obtain alkalitolerant actinomycete strains and their culture conditions. The active compounds were isolated by column chromatography over silica gel and Sephadex LH-20 and further purified by HPLC. The structural identification was performed by spectroscopic methods and X-ray diffraction. Results An alkalitolerant actinomycetes strain （OUCMDZ-1368） to produce phenazines was obtained and identified as Streptomyces sindenensis. The amounts of secondary metabolites of S. sindenensis OUCMDZ-1368 were the largest in a pH 9 culture medium, from which eleven compounds were isolated. And the structures were identified as phenazine-1- carboxamide （1）, phenazine-1-carboxylic acid （2）, （E）-2-non-1-en-1-yl-4（1H）quinolone （3）, 2-heptyl- 4（1H）quinolone （4）, 2-nonyl-4（1H）quinolone （5）, 2-undecyl-4（1H）quinolone （6）, 2-heptyl-3-hydroxy-4（1H）quinolone （7）, 2-nonyl-3-hydroxyl-4（1H）quinolone （8）, 2-methyl-4（1H） quinolone （9）, S-methyl-2,4-dihydroxy-3,5-dimethyl- 6-isopropylbenzothioate （10） and N-[2-（4- hydroxyphenyl）ethyl]acetamide （11）. Compounds 1 and 2 showed cytotoxicity on A549 cell line with the IC50 values of 4.9 and 5.0μmol/L, respectively. And compounds 1-10 exhibited antimicrobial activities against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Candida albicans with the MIC values of 17-45μmol/L. Conclusion The pH value of the culture media could affect the microbial secondary metabolites, and the regulation of pH values could induce microorganisms to produce different secondary metabolites.