本文選題：海洋鏈霉菌 + 深海真菌　； 參考：《浙江大學(xué)》2017年博士論文

【摘要】：本文對(duì)從溫州洞頭近海沉積物樣品和南海深海沉積物樣品中分離得到的121株菌的發(fā)酵粗提物進(jìn)行了細(xì)胞毒活性篩選,選擇其中兩株具有顯著細(xì)胞毒活性的菌株Streptomyces sp. DT-A37和Penicili m sp. NH-SL 以及 1 株代謝產(chǎn)物類型豐富的菌株Alternariasp.NH-F6進(jìn)行代謝產(chǎn)物系統(tǒng)分析,共分離鑒定了 46個(gè)化合物,其中9個(gè)為新化合物,并對(duì)所得化合物進(jìn)行了細(xì)胞毒活性測試、BRD4蛋白抑制活性測試、抗菌活性測試等生物活性評(píng)價(jià)。綜合運(yùn)用常壓硅膠柱色譜、反相高效制備液相色譜、凝膠柱色譜等方法對(duì)發(fā)酵提取物進(jìn)行分離純化,采用波譜技術(shù)鑒定化合物結(jié)構(gòu)。運(yùn)用OneStrain-Many Compounds (OSMAC)策略對(duì)鏈霉菌Streptomycessp. DT-A37的代謝產(chǎn)物進(jìn)行挖掘,從中分離鑒定了 10個(gè)化合物,包括4個(gè)新化合物(1Z)-S,S'-dimethyldihydro holomycin (2), holomycin A (3), cis-2'- (4"-hydroxy-4"-methylpenty1) - cyclo-propylacetic acid (4), cis-2'- (4", 5"-dihydroxy-4"-methylhexyl) -cyclopropylaceti acid (5),以及6個(gè)已知化合物。其中,holomycin (1)具有顯著的細(xì)胞毒活性和抗菌活性,其對(duì)H1975細(xì)胞的IC50值為1μM,對(duì)大腸桿菌和金黃色葡萄球菌的MIC值均為64 μM。從交鏈孢霉菌Alternariasp. NH-F6的固體發(fā)酵培養(yǎng)提取物中共分離鑒定了26 個(gè)化合物,包括 5 個(gè)新化合物 8β-chloro-3, 6aa, 7β, 9β,10-pentahydroxy-6, 6a,6b, 7, 8, 9-hexahydro-4 (5H) -one (11), 3, 7β, 8α, 9β, 10-pentahydroxy-7, 8-dihydroperylen-4 (9H) -one (12), 2- (N-vinylacetamide) -3-ene-4-hydroxymethy1-y-butyrolactone (13),alternarienonic acid B (15), chrysogeside F (17),以及 21個(gè)已知化合物。其中,化合物11和12具有顯著的BRD4蛋白抑制活性,IC50值分別為11.8 μM和7.1 μM�；衔�12具有明顯的抗菌活性,其對(duì)大腸桿菌和金黃色葡萄球菌的MIC值分別為16 μM和32 μM。從青霉菌Penicilliumsp. NH-SL的液體發(fā)酵培養(yǎng)提取物中共分離鑒定了 10個(gè)化合物,其中具有異戊烯基取代的吲哚生物堿類化合物verrucofortine (38)表現(xiàn)出顯著的細(xì)胞毒活性,其在測試濃度為0.7 μM時(shí)對(duì)Hepa lclc7細(xì)胞的抑制率為85.8 %。采用多級(jí)質(zhì)譜法對(duì)該化合物進(jìn)行裂解規(guī)律的研究,并根據(jù)其裂解規(guī)律,從該菌株的總提取物中檢測到其它三個(gè)異戊烯基吲哚生物堿類似物47～49,為異戊烯基吲哚生物堿類化合物的快速發(fā)現(xiàn)提供了參考依據(jù)。
[Abstract]:In this paper, the fermentation crude extracts of 121 strains isolated from Dongtou offshore sediment samples and deep-sea sediment samples from the South China Sea were screened for cytotoxicity, and two of them, Streptomyces spp., were selected. DT-A37 and Penicili m sp. NH-SL and Alternariasp.NH-F6, a strain with abundant metabolites, were analyzed systematically. A total of 46 compounds were isolated and identified, 9 of which were new compounds. The cytotoxic activity of the compounds was evaluated by BRD4 protein inhibition test and antimicrobial activity test. The fermentation extract was separated and purified by atmospheric pressure silica gel column chromatography, reversed phase high performance liquid chromatography and gel column chromatography. The structure of the compound was identified by spectroscopic technique. Streptomyces spp. Ten compounds were isolated and identified from the metabolites of DT-A37, including four new compounds, namely, four new compounds, one new compound, one, two, four, five, four, four Its IC50 value to H1975 cells was 1 渭 M, and the MIC value to Escherichia coli and Staphylococcus aureus was 64 渭 M. Alternaria sp. from Alternaria alternata. NH-F6鐨勫浐浣撳彂閰靛煿鍏繪彁鍙栫墿涓叡鍒嗙閴村畾浜，

本文編號(hào)：1885835