摘要
【目的】从黄河三角洲耐盐微生物的代谢产物中寻找具有抗菌和抗肿瘤活性的化合物。【方法】应用化学与生物活性相集成的筛选方法,从耐盐微生物中筛选获得代谢产物丰富并具有生物活性的目标菌株;通过高盐胁迫目标菌株,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、纯化,运用波谱解析、钼靶X-射线单晶衍射分析、圆二色散谱(CD)和密度泛函数(DFT)-ECD的计算鉴定化合物的结构。【结果】从采自黄河三角洲的泥土样品中得到一株耐盐真菌HK14-01,鉴定为产黄青霉Penicilliumchrysogenum;从其发酵产物中分离鉴定了8个化合物:(2S,3R)-oxaline(1,主产物)、(3R,4R)-3,4,8-trihydroxy-3,4-dihydronaphthalen-1(2H)-one(2)、(Z)-N-(4-hydroxystyryl)formamide(3)、(E)-N-(4-hydroxystyryl)formamide(4)、emodin(5)、4-(2-hydroxyethyl)benzene-1,2-diol(6)、methyl 2-(4-hydroxyphenyl)acetate(7)和2-(4-hydroxy phenyl)acetonitrile(8);化合物1、3和4对大肠杆菌以及化合物1和5对金黄色葡萄球菌表现出抑菌活性,化合物5对P388细胞表现出微弱的细胞增殖抑制活性。【结论】首次确定了化合物2的绝对构型、首次报道了化合物1和2的CD数据;从黄河三角洲的耐盐微生物的次生代谢产物中可以得到活性化合物,这一区域的耐盐微生物资源值得深入研究。
[Objective] To search for structurally novel and biologically active compounds from the secondary metabolites of halotolerant fungi from the Yellow River Delta area.[Methods] We screened halotolerant fungi with rich chemical diversity and antitumor or antimicrobial activity by means of integrated chemical and biological method.We cultured halotolerant fungi under different conditions at first.Then we investigated the chemical diversity and the bioactivity of the EtOAc extracts of the fermentation broth by HPLC and TLC,and cytotoxic assay or antimicrobial assay.We selected Penicillium chrysogenum HK14-01 to further study for the large yield,producing alkaloids and cytotoxicity on P388 cells in YMDP culture medium containing 10% NaCl.We fermented P.chrysogenum HK14-01 on a large scale;we isolated and purified the compounds by column chromatography over silica gel,Sephadex LH-20,and semipreparative HPLC;and we identified the structures by spectroscopic analysis,X-ray diffraction（Mo-Kα）,CD spectra and the time-dependent density functional theory electronic circular dichroism（TDDFT ECD） calculation.[Results]We isolated and identified a halotolerant fungal strain,P.chrysogenum HK14-01,from the sediments collected in the Yellow River Delta area.From the fermentation broth of P.chrysogenum HK14-01,we isolated and identified eight compounds,i.e.（2S,3R）-oxaline（1,a major product）,（3R,4R）-3,4,8-trihydroxy-3,4-dihydronaphthalen-1（2H）-one（2）,（Z）-N-（4-hydroxy styryl）formamide（3）,（E）-N-（4-hydroxystyryl）formamide（4）,emodin（5）,4-（2-hydroxyethyl）benzene-1,2-diol（6）,methyl 2-（4-hydroxyphenyl）acetate（7）,and 2-（4-hydroxyphenyl）acetonitrile（8）.[Conclusion] Bioactive compounds can be obtained from the secondary metabolites of halotolerant microorganisms from the Yellow River Delta area.
出处
《微生物学报》
CAS
CSCD
北大核心
2012年第9期1103-1112,共10页
Acta Microbiologica Sinica
基金
国家"973项目"(2010CB833800)
国家自然科学基金(21172204)
山东省自然科学基金(ZR2009CQ030)~~
关键词
黄河三角洲
耐盐真菌
产黄青霉
次生代谢
抗菌活性
Yellow River Delta
halotolerant fungus
Penicillium chrysogenum
secondary metabolites
antimicrobial activity
