海绵真菌Myrothecium verrucaria Hmp-F73代谢产物及其生物活性研究
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摘要
海绵的种类繁多,分布广泛,能产生大量的生物活性物质,据统计现已报道的海洋天然产物中,来源于海绵的占40.6 %。近年的研究表明许多海绵天然产物由其共附生微生物产生,这些微生物被认为是活性物质的真正来源。虽然海绵采集困难,活性成分含量不高,但是海绵共附生微生物可以进行大量培养发酵,从而可以低成本大规模生产有价值的天然产物。所以海绵共附生微生物的研究已经逐渐成为海绵天然产物研究的重要部分。
本论文拟从海绵共附生微生物资源中筛选出具有良好杀虫活性的菌株,探索结构新颖具有潜在价值的杀虫活性物质。本论文使用卤虫生物检测法作为杀虫活性检测模型,从98株海绵共附生丝状真菌中,筛选得到一株活性丝状真菌Hmp-F73,经鉴定为Myrothecium verrucaria。该菌发酵产物对卤虫具有较强杀虫活性,发酵液的甲醇提取物浓度为0.25μg/mL时,对卤虫的校正死亡率为100.00 %;甲醇提取物经硅胶柱层析洗脱得到7个馏分,其中馏分3浓度为400μg/mL时对甜菜夜蛾具有明显抑制取食活性,拒食率达到85.25 %;馏分6浓度为1 mg/mL时对玉米纹枯病菌Rhizoctonia solani抑菌圈直径达9.25 mm。通过活性追踪的方法,进一步分离纯化得到7个单端孢霉烯族毒素类物质,分别为:Verrucarin J (化合物1),Isororidin E (2),Roridin E (3),8-acetoxyroridin H (4),8-hydroxyverrucarin J (5),Trichoverrin B (6),Verrucarin A (7)。这些化合物对卤虫的LC50值为0.001~1.138μg/mL。植物毒性实验结果表明,所有的化合物在浓度为1μg/mL时对生菜种子的萌发没有抑制作用,直到浓度增加为100μg/mL时化合物2,3和6才表现出轻微的抑制作用。
单端孢霉烯族化合物其基本结构是倍半萜烯,在杀虫活性方面的研究报道比较少。本论文筛选得到的这株海洋真菌Hmp-F73由于其代谢产物具有很好杀虫活性并且对植物几乎没有毒性,因此具有潜在的开发研究价值,可以作为新的杀虫微生物资源。我们对该菌代谢产物进行分离纯化,确定其化学结构和生物活性,并对这些产物的结构与活性之间的构效关系做了简单的推测。
Sponges are widely distributed with wide varieties, and could produce a large number of biologically active substances. Among the marine natural products reported, 40.6 % of them were isolated from sponge. Recent studies suggest that some sponge natural products were produced by their symbiotic microbe. Due to the difficulty for collecting sponge and their lower level of active ingredient, cultivation of sponge symbiotic microbe in large scale cultivation was a plausible way to produce valuable natural products. So the research on chemical constituents from sponge symbiotic microbe has become popular in marine natural products.
This thesis was planned to screening insecticidal microbe from sponge symbiotic microbe resources, in order to find potentially insecticidal agents. As a result, a strain Hmp-F73 was selected and identified as Myrothecium verrucaria according to the Brine Shrimp insecticidal assay on 96 fungal strains derived from sponge. When the concentration of the methanolic extract of Hmp-F73 was 0.25μg/mL, the corrected mortality was 100.00 %. The methanolic extract was portioned with silica gel column chromatography, and 7 fractions were obtained. At the concentration of 400μg/mL of fraction 3, it could inhibit the feeding of Spodoptera exigu by the rate of 85.25 %. The fraction 6 at 1 mg/mL also demonstrated significant inhibition activity against Rhizoctonia solani with 9.25 mm of inhibition zone. Seven macrocyclic trichothecenes were purified by tracking the activity: Verrucarin J (Compound 1), Isororidin E (2), Roridin E (3), 8-acetoxyroridin H (4), 8-hydroxyverrucarin J (5), Trichoverrin B (6), Verrucarin A (7). All the metabolites displayed potent toxic activity with LC50 values ranging from 0.001μg/mL to 1.138μg/ml. And all the compounds showed no toxicity on lettuce seeds at 1μg/ml, while a weak toxicity at 100μg/ml.
Trichothecenes comprise a group of sesquiterpenes characterized structurally by the 12, 13-epoxy-trichothec-9-ene moiety. However, there are few report related with insecticidal activity of these mycotoxins. This thesis found that the marine fungus Hmp-F73 could be considered as a resource of microbial pesticide without toxicity to plants. In this study we have investigated the production, the chemical purification, and the chemical and biological characterization of the metabolites produced by Myrothecium verrucaria. A preliminary structure–activity relationship of the insecticidal trichothecenes was highlighted in brief.
本论文拟从海绵共附生微生物资源中筛选出具有良好杀虫活性的菌株,探索结构新颖具有潜在价值的杀虫活性物质。本论文使用卤虫生物检测法作为杀虫活性检测模型,从98株海绵共附生丝状真菌中,筛选得到一株活性丝状真菌Hmp-F73,经鉴定为Myrothecium verrucaria。该菌发酵产物对卤虫具有较强杀虫活性,发酵液的甲醇提取物浓度为0.25μg/mL时,对卤虫的校正死亡率为100.00 %;甲醇提取物经硅胶柱层析洗脱得到7个馏分,其中馏分3浓度为400μg/mL时对甜菜夜蛾具有明显抑制取食活性,拒食率达到85.25 %;馏分6浓度为1 mg/mL时对玉米纹枯病菌Rhizoctonia solani抑菌圈直径达9.25 mm。通过活性追踪的方法,进一步分离纯化得到7个单端孢霉烯族毒素类物质,分别为:Verrucarin J (化合物1),Isororidin E (2),Roridin E (3),8-acetoxyroridin H (4),8-hydroxyverrucarin J (5),Trichoverrin B (6),Verrucarin A (7)。这些化合物对卤虫的LC50值为0.001~1.138μg/mL。植物毒性实验结果表明,所有的化合物在浓度为1μg/mL时对生菜种子的萌发没有抑制作用,直到浓度增加为100μg/mL时化合物2,3和6才表现出轻微的抑制作用。
单端孢霉烯族化合物其基本结构是倍半萜烯,在杀虫活性方面的研究报道比较少。本论文筛选得到的这株海洋真菌Hmp-F73由于其代谢产物具有很好杀虫活性并且对植物几乎没有毒性,因此具有潜在的开发研究价值,可以作为新的杀虫微生物资源。我们对该菌代谢产物进行分离纯化,确定其化学结构和生物活性,并对这些产物的结构与活性之间的构效关系做了简单的推测。
Sponges are widely distributed with wide varieties, and could produce a large number of biologically active substances. Among the marine natural products reported, 40.6 % of them were isolated from sponge. Recent studies suggest that some sponge natural products were produced by their symbiotic microbe. Due to the difficulty for collecting sponge and their lower level of active ingredient, cultivation of sponge symbiotic microbe in large scale cultivation was a plausible way to produce valuable natural products. So the research on chemical constituents from sponge symbiotic microbe has become popular in marine natural products.
This thesis was planned to screening insecticidal microbe from sponge symbiotic microbe resources, in order to find potentially insecticidal agents. As a result, a strain Hmp-F73 was selected and identified as Myrothecium verrucaria according to the Brine Shrimp insecticidal assay on 96 fungal strains derived from sponge. When the concentration of the methanolic extract of Hmp-F73 was 0.25μg/mL, the corrected mortality was 100.00 %. The methanolic extract was portioned with silica gel column chromatography, and 7 fractions were obtained. At the concentration of 400μg/mL of fraction 3, it could inhibit the feeding of Spodoptera exigu by the rate of 85.25 %. The fraction 6 at 1 mg/mL also demonstrated significant inhibition activity against Rhizoctonia solani with 9.25 mm of inhibition zone. Seven macrocyclic trichothecenes were purified by tracking the activity: Verrucarin J (Compound 1), Isororidin E (2), Roridin E (3), 8-acetoxyroridin H (4), 8-hydroxyverrucarin J (5), Trichoverrin B (6), Verrucarin A (7). All the metabolites displayed potent toxic activity with LC50 values ranging from 0.001μg/mL to 1.138μg/ml. And all the compounds showed no toxicity on lettuce seeds at 1μg/ml, while a weak toxicity at 100μg/ml.
Trichothecenes comprise a group of sesquiterpenes characterized structurally by the 12, 13-epoxy-trichothec-9-ene moiety. However, there are few report related with insecticidal activity of these mycotoxins. This thesis found that the marine fungus Hmp-F73 could be considered as a resource of microbial pesticide without toxicity to plants. In this study we have investigated the production, the chemical purification, and the chemical and biological characterization of the metabolites produced by Myrothecium verrucaria. A preliminary structure–activity relationship of the insecticidal trichothecenes was highlighted in brief.
引文
丁常荣. 2005.微生物农药及其应用前景.北京农业, 7: 34~34
方玉春,李凌绪,朱天骄,蔡生新,顾谦群,朱伟明,王长云,郝双红. 2009.海绵微生物的分离培养及一种活性代谢产物的初步研究.中国海洋大学学报(自然科学版), (04): 742~744
王祥敏,李明,骆祝华,赵昌会,黄翔玲,叶德赞. 2007.海洋真菌及其生物活性物质多样性研究. 海洋湖沼通报, (03): 69~74
田黎,陈杰,何运转,田玲. 2003a.农用抗生素的新资源――海洋微生物.中国生物防治, 19(3): 121~124
田黎,顾振芳等. 2003b.海洋细菌b―9987菌株产生的抑菌物质及对几种植物病原真菌的作用. 植物病理学报, 33(1): 77~80
石志琦,范永坚等. 2002.天然化合物在农药中的应用研究.江苏农业学报, 18(4): 241~245
李利君,蔡慧农. 2000.海洋微生物生物活性物质的研究.集美大学学报:自然科学版, 5(2): 80~86
胡军,杨军艳,张继宏. 1997.胆红素氧化酶产生菌的选育及发酵工艺条件的研究.食品与发酵工业, 33(02): 22~25
徐守健,张久明,田黎,罗万春. 2006.海洋微生物杀虫活性筛选方法比较.华东昆虫学报, (01): 70~74
徐伟松,李建丰,胡美英. 2003.昆虫病原真菌在害虫防治上的应用.广西农业科学, 6: 51~52
彭双清. 1994.单端孢霉烯族真菌毒素及其毒性.动物毒物学, 9(1): 25~29
魏景超. 1979.真菌鉴定手册.
刘永全,胡江春等. 2002.海洋微生物生物活性物质研究.应用生态学报, 13(7): 901~905
刘雪莉,钱伯初. 1997.日本海洋天然活性物质研究简况.中国海洋药物, (01): 45~49
刘济宁,余向阳,张存政,洪葵,彭正强,刘贤进. 2004.具有杀虫活性的海洋微生物的筛选.江苏农业学报, 20(2): 84~86
吴文平. 1991.河北省丝孢菌研究Ⅲ、漆斑菌属(Myrothecium Tode:Fr.)的四个种.河北省科学院学报, 1(01): 69~74
吴秀丽,王艳,赵文倩,张怡轩. 2008.一种真菌对人参皂苷Rg_3的转化.微生物学报, 48(09): 1181~1185
张炳火,方亮,李汉全,过七根. 2006.微生物资源研究开发进展.国外医药(抗生素分册), (05): 233~235
盖悦. 2007.海绵共附生系状菌中生物活性物质的研究. [博士学位论文].上海:复旦大学
黄孝春,郭跃伟. 2005.海绵药物的研究进展:化学和生物活性.中国天然药物, 3(1): 1~9
黄丽波,徐石海等. 2001.海绵中抗肿瘤抗病毒生物活性的生物碱研究进展.广州医药, 32(1): 2~5
Abbas H K, Johnson B B, Shier W T, Tak H, Jarvis B B, Boyette C D. 2002. Phytotoxicity and mammalian cytotoxicity of macrocyclic trichothecene mycotoxins from Myrothecium verrucaria. Phytochemistry, 59(3): 309~313
Abraham E, Loder P B. 1972. Cephalosporin C.in Cephalosporins and Penicillins:Chemistry andBiology. ed. E. H. Flynn. New York Green
Alvi K A, Rabenstein J, Woodard J, Baker D D, Bergthold J D, Lynch J, Lieu K L, Braude I A. 2002. 14 '-hydroxymytoxin B and 16-hydroxyroridin E, two new cytotoxic trichothecenes from Myrothecium roridum. Journal of Natural Products, 65(5): 742~744
Amagata T, Rath C, Rigot J F, Tarlov N, Tenney K, Valeriote F A, Crews P. 2003. Structures and cytotoxic properties of trichoverroids and their macrolide analogues produced by saltwater culture of Myrothecium verrucaria. Journal of Medicinal Chemistry, 46(20): 4342~4350
Andolfi A, Boari A, Evidente A, Vurro M. 2005. Metabolites inhibiting germination of Orobanche ramosa seeds produced by Myrothecium verrucaria and Fusarium compactum. Journal of Agricultural and Food Chemistry, 53(5): 1598~1603
Bewley C A, Faulkner D J. 1998. Lithistid sponges: Star performers or hosts to the stars. Angewandte Chemie-International Edition, 37(16): 2163~2178
Blunt J W, Copp B R, Hu W P, Munro M H G, Northcote P T, Prinsep M R. 2009. Marine natural products. Natural Product Reports, 26(2): 170~244
Breitenstein W, Tamm C. 1975. C-13 Nmr.-Spectroscopy of Trichothecane Derivatives Verrucarol, Verrucarin-a and Verrucarin-B and Roridins-a, Roridin-D and Roridins-H. Helvetica Chimica Acta, 58(4): 1172~1180
Breitenstein W, Tamm C. 1978. Verrucarine and Voridine 35 Partial Synthesis of Tetrahydro verrucarin-J. Helvetica Chimica Acta, 61(6): 1975~1983
Bretz M, Beyer M, Cramer B, Knecht A, Humpf H U. 2006. Thermal degradation of the Fusarium mycotoxin deoxynivalenol. Journal of Agricultural and Food Chemistry, 54(17): 6445~6451
Capon R J, Skene C, Stewart M, Ford J, O'Hair R A J, Williams L, Lacey E, Gill J H, Heiland K, Friedel T. 2003. Aspergillicins A-E: five novel depsipeptides from the marine-derived fungus Aspergillus carneus. Organic & Biomolecular Chemistry, 1(11): 1856~1862
Chinworrungsee M, Wiyakrutta S, Sriubolmas N, Chuailua P, Suksamrarn A. 2008. Cytotoxic activities of trichothecenes isolated from an endophytic fungus belonging to order hypocreales. Archives of Pharmacal Research, 31(5): 611~616
Choi S U, Choi E J, Kim K H, Kim N Y, Kwon B M, Kim S U, Bok S H, Lee S Y, Lee C O. 1996. Cytotoxicity of trichothecenes to human solid tumor cells in vitro. Archives of Pharmacal Research, 19(1): 6~11
Desjardins A E, McCormick S P, Appell M. 2007. Structure-activity relationships of trichothecene toxins in an Arabidopsis thaliana leaf assay. Journal of Agricultural and Food Chemistry, 55(16): 6487~6492
Dorit R L W F, Barnes R D. 1991. Zoology: 1009~1011
Eppley R M, Mazzola E P, Highet R J, Bailey W J. 1977. Structure of Satratoxin H, a Metabolite of Stachybotrys-Atra - Application of Proton and C-13 Nuclear Magnetic-Resonance. Journal of Organic Chemistry, 42(2): 240~243
Faulkner D J, Harper M K, Haygood M G, Salomon C E, Schmidt E W. 2000. Symbiotic bacteria in sponges: sources of bioactive substances. Drugs from the sea: 107~119
Fetz E, Bohner B, Tamm C. 1965. Die Konstitution Von Verrucarin J. Helvetica Chimica Acta, 48(7): 1669~&
Gnanamani A, Kavitha V, Radhakrishnan N, Rajakumar G S, Sekaran G, Mandal A B. 2010. Microbial products (biosurfactant and extracellular chromate reductase) of marine microorganism are the potential agents reduce the oxidative stress induced by toxic heavy metals. Colloids and Surfaces B-Biointerfaces, 79(2): 334~339
Halliwell G. 1961. Action of Cellulolytic Enzymes from Myrothecium Verrucaria. Biochemical Journal, 79(1): 185~192
Jarvis B B, Desilva T, Mcalpine J B, Swanson S J, Whittern D N. 1992. New Trichoverroids from Myrothecium-Verrucaria Isolated by High-Speed Countercurrent Chromatography. Journal of Natural Products, 55(10): 1441~1446
Jarvis B B, Midiwo J O, Desilva T. 1981. Verrucarin-L, a New Macrocyclic Trichothecene. Journal of Antibiotics, 34(1): 120~121
Jarvis B B, Midiwo J O, Mazzola E P. 1984. Antileukemic Compounds Derived by Chemical Modification of Macrocyclic Trichothecenes .2. Derivatives of Roridin-a and Roridin-H and Verrucarin-a and Verrucarin-J. Journal of Medicinal Chemistry, 27(2): 239~244
Jarvis B B, Wang S J. 1999. Stereochemistry of the roridins. Diastereomers of roridin E. Journal of Natural Products, 62(9): 1284~1289
Jin H Z, Lee J H, Zhang W D, Lee H B, Hong Y S, Kim Y H, Lee J J. 2007. Harzianums A and B produced by a fungal strain, Hypocrea sp. F000527, and their cytotoxicity against tumor cell lines. Journal of Asian Natural Products Research, 9(3): 203~207
Kikuchi H, Miyagawa Y, Nakamura K, Sahashi Y, Inatomi S, Oshima Y. 2004a. A novel carbon skeletal trichothecane, tenuipesine A, isolated from an entomopathogenic fungus, Paecilomyces tenuipes. Organic Letters, 6(24): 4531~4533
Kikuchi H, Miyagawa Y, Sahashi Y, Inatomi S, Haganuma A, Nakahata N, Oshima Y. 2004b. Novel spirocyclic trichothecanes, spirotenuipesine A and B, isolated from entomopathogenic fungus, Paecilomyces tenuipes. Journal of Organic Chemistry, 69(2): 352~356
Kikuchi H, Miyagawa Y, Sahashi Y, Inatomi S, Haganuma A, Nakahata N, Oshima Y. 2004c. Novel trichothecanes, paecilomycine A, B, and C, isolated from entomopathogenic fungus, Paecilomyces tenuipes. Tetrahedron Letters, 45(33): 6225~6228
Konishi K, Iida A, Kaneko M, Tomioka K, Tokuda H, Nishino H, Kumeda Y. 2003. Cancer preventive potential of trichothecenes from Trichothecium roseum. Bioorganic & Medicinal Chemistry, 11(12): 2511~2518
Koyama K, Ishino M, Takatori K, Sugita T, Kinoshita K, Takahashi K. 2004. Phomactin H, a novel diterpene from an unidentified marine-derived fungus. Tetrahedron Letters, 45(37): 6947~6948
Krohn K, Steingrover K, Aust H J, Draeger S, Schulz B. 2003. Biologically active metabolites from fungi, 17. 8-alpha-acetoxyverrol, a new member of the trichothecene sesquiterpenes. Natural Product Research, 17(1): 67~70
Laurent D, Guella G, Roquebert M F, Farinole F, Mancini I, Pietra F. 2000. Cytotoxins, mycotoxins and drugs from a new deuteromycete, Acremonium neo-caledoniae, from the southwestern lagoon of New Caledonia. Planta Medica, 66(1): 63~66
Liu J Y, Huang L L, Ye Y H, Zou W X, Guo Z J, Tan R X. 2006. Antifungal and new metabolites of Myrothecium sp Z16, a fungus associated with white croaker Argyrosomus argentatus. Journal of AppliedMicrobiology, 100(1): 195~202
Madhyastha M S, Marquardt R R, Abramson D. 1994. Structure-Activity-Relationships and Interactions among Trichothecene Mycotoxins as Assessed by Yeast Bioassay. Toxicon, 32(9): 1147~1152
Meyer S W, Mordhorst T F, Lee C, Jensen P R, Fenical W, Kock M. 2010. Penilumamide, a novel lumazine peptide isolated from the marine-derived fungus, Penicillium sp CNL-338. Organic & Biomolecular Chemistry, 8(9): 2158~2163
Murakami Y, Okuda T, Shindo K. 2001. Roridin L, M and Verrucarin M, new macrocyclic trichothecene group antitumor antibiotics, from Myrothecium verrucaria. Journal of Antibiotics, 54(11): 980~983
Murao S, Tanaka N. 1981. A New Enzyme Bilirubin Oxidase Produced by Myrothecium-Verrucaria Mt-1. Agricultural and Biological Chemistry, 45(10): 2383~2384
Murao S, Tanaka N. 1982. Isolation and Identification of a Microorganism Producing Bilirubin Oxidase. Agricultural and Biological Chemistry, 46(8): 2031~2034
Muroga Y, Yamada T, Numata A, Tanaka R. 2010. 11-and 4 '-Epimers of Chaetomugilin A, Novel Cytostatic Metabolites from Marine Fish-Derived Fungus Chaetomium globosum. Helvetica Chimica Acta, 93(3): 542~549
Namikoshi M, Akano K, Meguro S, Kasuga I, Mine Y, Takahashi T, Kobayashi H. 2001. A new macrocyclic trichothecene, 12,13-deoxyroridin E, produced by the marine-derived fungus Myrothecium roridum collected in Palau. Journal of Natural Products, 64(3): 396~398
Nicholson G M. 2007. Fighting the global pest problem: Preface to the special Toxicon issue on insecticidal toxins and their potential for insect pest control. Toxicon, 49(4): 413~422
Nitao J K, Meyer S L F, Schmidt W F, Fettinger J C, Chitwood D J. 2001. Nematode-antagonistic trichothecenes from Fusarium equiseti. Journal of Chemical Ecology, 27(5): 859~869
Oclarit J M, Belarmino I B M, Ieee. 2009. Quantitative analysis of omega-3 aliphatic acid from schizochytrium sp. dzam (order thraustochytriales division chromista) under different spectral photo-emissions. Oceans 2009 - Europe, Vols 1 and 2. New York, Ieee: 5~11
Ren S, Ma W, Xu T H, Lin X P, Yin H, Yang B, Zhou X F, Yang X W, Long L J, Lee K J, Gao Q P, Liu Y H. 2010. Two novel alkaloids from the South China Sea marine sponge Dysidea sp. Journal of Antibiotics, 63(12): 699~701
Saikawa Y, Okamoto H, Inui T, Makabe M, Okuno T, Suda T, Hashimoto K, Nakata M. 2001. Toxic principles of a poisonous mushroom Podostroma cornu-damae. Tetrahedron, 57(39): 8277~8281
Schoettler S, Bascope M, Sterner O, Anke T. 2006. Isolation and characterization of two verrucarins from Myrothecium roridum. Zeitschrift Fur Naturforschung C-a Journal of Biosciences, 61(5-6): 309~314
Shen L, Jiao R H, Ye Y H, Wang X T, Xu C, Song Y C, Zhu H L, Tan R X. 2006. Absolute configuration of new cytotoxic and other bioactive trichothecene macrolides. Chemistry-a European Journal, 12(21): 5596~5602
Shen L, Wang J A S, Shen H J, Song Y C, Tan R X. 2010. A New Cytotoxic Trichothecene Macrolide from the Endophyte Myrothecium roridum. Planta Medica, 76(10): 1004~1006
Sivapathasekaran C, Das P, Mukherjee S, Saravanakumar J, Mandal M, Sen R. 2010. Marine Bacterium Derived Lipopeptides: Characterization and Cytotoxic Activity Against Cancer Cell Lines. International Journal of Peptide Research and Therapeutics, 16(4): 215~222
Stierle A C, Cardellina J H, Singleton F L. 1988. A Marine Micrococcus Produces Metabolites Ascribed to the Sponge Tedania-Ignis. Experientia, 44(11-12): 1021~1021
Sugawara T, Tanaka A, Nagai K, Suzuki K, Okada G. 1997. New members of the trichothecene family. Journal of Antibiotics, 50(9): 778~780
Sugitakonishi Y, Kumagai S, Mizuochi T. 1994. The Cytotoxicity of Macrocyclic Trichothecenes, Roridin-a and Verrucarin-a, on Murine T-Cells Is Reduced by Ia-Negative Splenic Adherent Cells. Toxicon, 32(9): 1051~1057
Suzumura K, Yokoi T, Funatsu M, Nagai K, Tanaka K, Zhang H P, Suzuki K. 2003. YM-266183 and YM-266184, novel thiopeptide antibiotics produced by Bacillus cereus isolated from a marine sponge - II. Structure elucidation. Journal of Antibiotics, 56(2): 129~134
Thompson W L, Wannemacher R W. 1986. Structure-Function-Relationships of 12,13-Epoxytrichothecene Mycotoxins in Cell-Culture-Comparison to Whole Animal Lethality. Toxicon, 24(10): 985~994
Tiepo E N, Correa A X R, Resgalla C, Cotelle S, Ferard J F, Radetski C M. 2010. Terrestrial short-term ecotoxicity of a green formicide. Ecotoxicology and Environmental Safety, 73(5): 939~943
Wagenaar M M, Clardy J. 2001a. Dicerandrols, new antibiotic and cytotoxic dimers produced by the fungus Phomopsis longicolla isolated from an endangered mint. Journal of Natural Products, 64(8): 1006~1009
Wagenaar M M, Clardy J. 2001b. Two new roridins isolated from Myrothecium sp. Journal of Antibiotics, 54(6): 517~520
Wang T, Zhang Y, Pei Y H. 2007. Two novel trichothecenes from Myrothecium roridum. Medicinal Chemistry Research, 16(4): 155~161
Wright A D, McCluskey A, Robertson M J, MacGregor K A, Gordon C P, Guenther J. 2011. Anti-malarial, anti-algal, anti-tubercular, anti-bacterial, anti-photosynthetic, and anti-fouling activity of diterpene and diterpene isonitriles from the tropical marine sponge Cymbastela hooperi. Organic & Biomolecular Chemistry, 9(2): 400~407
Wu Q X, Crews M S, Draskovic M, Sohn J, Johnson T A, Tenney K, Valeriote F A, Yao X J, Bjeldanes L F, Crews P. 2010. Azonazine, a Novel Dipeptide from a Hawaiian Marine Sediment-Derived Fungus, Aspergillus insulicola. Organic Letters, 12(20): 4458~4461
Xie L W, Jiang S M, Zhu H H, Sun W, Ouyang Y C, Dai S K, Li X. 2008. Potential inhibitors against Sclerotinia sclerotiorum, produced by the fungus Myrothecium sp associated with the marine sponge Axinella sp. European Journal of Plant Pathology, 122(4): 571~578
Xu J Z, Takasaki A, Kobayashi H, Oda T, Yamada J, Mangindaan R E P, Ukai K, Nagai H, Namikoshi M. 2006. Four new macrocyclic trichothecenes from two strains of marine-derived fungi of the genus Myrothecium. Journal of Antibiotics, 59(8): 451~455
Yu N J, Guo S X, Lu H Y. 2002. Cytotoxic macrocyclic trichothecenes from the mycelia of Calcarisporium arbuscula Preuss. Journal of Asian Natural Products Research, 4(3): 179~183
Zhang D J, Liu R F, Li Y G, Tao L M, Tian L. 2010. Two New Antifungal Cyclic Lipopeptides from Bacillus marinus B-9987. Chemical & Pharmaceutical Bulletin, 58(12): 1630~1634
Zhang Y, Wang T, Pei Y H, Hua H M, Feng B M. 2002. Aspergillin PZ, a novel isoindole-alkaloid from Aspergillus awamori. Journal of Antibiotics, 55(8): 693~695
方玉春,李凌绪,朱天骄,蔡生新,顾谦群,朱伟明,王长云,郝双红. 2009.海绵微生物的分离培养及一种活性代谢产物的初步研究.中国海洋大学学报(自然科学版), (04): 742~744
王祥敏,李明,骆祝华,赵昌会,黄翔玲,叶德赞. 2007.海洋真菌及其生物活性物质多样性研究. 海洋湖沼通报, (03): 69~74
田黎,陈杰,何运转,田玲. 2003a.农用抗生素的新资源――海洋微生物.中国生物防治, 19(3): 121~124
田黎,顾振芳等. 2003b.海洋细菌b―9987菌株产生的抑菌物质及对几种植物病原真菌的作用. 植物病理学报, 33(1): 77~80
石志琦,范永坚等. 2002.天然化合物在农药中的应用研究.江苏农业学报, 18(4): 241~245
李利君,蔡慧农. 2000.海洋微生物生物活性物质的研究.集美大学学报:自然科学版, 5(2): 80~86
胡军,杨军艳,张继宏. 1997.胆红素氧化酶产生菌的选育及发酵工艺条件的研究.食品与发酵工业, 33(02): 22~25
徐守健,张久明,田黎,罗万春. 2006.海洋微生物杀虫活性筛选方法比较.华东昆虫学报, (01): 70~74
徐伟松,李建丰,胡美英. 2003.昆虫病原真菌在害虫防治上的应用.广西农业科学, 6: 51~52
彭双清. 1994.单端孢霉烯族真菌毒素及其毒性.动物毒物学, 9(1): 25~29
魏景超. 1979.真菌鉴定手册.
刘永全,胡江春等. 2002.海洋微生物生物活性物质研究.应用生态学报, 13(7): 901~905
刘雪莉,钱伯初. 1997.日本海洋天然活性物质研究简况.中国海洋药物, (01): 45~49
刘济宁,余向阳,张存政,洪葵,彭正强,刘贤进. 2004.具有杀虫活性的海洋微生物的筛选.江苏农业学报, 20(2): 84~86
吴文平. 1991.河北省丝孢菌研究Ⅲ、漆斑菌属(Myrothecium Tode:Fr.)的四个种.河北省科学院学报, 1(01): 69~74
吴秀丽,王艳,赵文倩,张怡轩. 2008.一种真菌对人参皂苷Rg_3的转化.微生物学报, 48(09): 1181~1185
张炳火,方亮,李汉全,过七根. 2006.微生物资源研究开发进展.国外医药(抗生素分册), (05): 233~235
盖悦. 2007.海绵共附生系状菌中生物活性物质的研究. [博士学位论文].上海:复旦大学
黄孝春,郭跃伟. 2005.海绵药物的研究进展:化学和生物活性.中国天然药物, 3(1): 1~9
黄丽波,徐石海等. 2001.海绵中抗肿瘤抗病毒生物活性的生物碱研究进展.广州医药, 32(1): 2~5
Abbas H K, Johnson B B, Shier W T, Tak H, Jarvis B B, Boyette C D. 2002. Phytotoxicity and mammalian cytotoxicity of macrocyclic trichothecene mycotoxins from Myrothecium verrucaria. Phytochemistry, 59(3): 309~313
Abraham E, Loder P B. 1972. Cephalosporin C.in Cephalosporins and Penicillins:Chemistry andBiology. ed. E. H. Flynn. New York Green
Alvi K A, Rabenstein J, Woodard J, Baker D D, Bergthold J D, Lynch J, Lieu K L, Braude I A. 2002. 14 '-hydroxymytoxin B and 16-hydroxyroridin E, two new cytotoxic trichothecenes from Myrothecium roridum. Journal of Natural Products, 65(5): 742~744
Amagata T, Rath C, Rigot J F, Tarlov N, Tenney K, Valeriote F A, Crews P. 2003. Structures and cytotoxic properties of trichoverroids and their macrolide analogues produced by saltwater culture of Myrothecium verrucaria. Journal of Medicinal Chemistry, 46(20): 4342~4350
Andolfi A, Boari A, Evidente A, Vurro M. 2005. Metabolites inhibiting germination of Orobanche ramosa seeds produced by Myrothecium verrucaria and Fusarium compactum. Journal of Agricultural and Food Chemistry, 53(5): 1598~1603
Bewley C A, Faulkner D J. 1998. Lithistid sponges: Star performers or hosts to the stars. Angewandte Chemie-International Edition, 37(16): 2163~2178
Blunt J W, Copp B R, Hu W P, Munro M H G, Northcote P T, Prinsep M R. 2009. Marine natural products. Natural Product Reports, 26(2): 170~244
Breitenstein W, Tamm C. 1975. C-13 Nmr.-Spectroscopy of Trichothecane Derivatives Verrucarol, Verrucarin-a and Verrucarin-B and Roridins-a, Roridin-D and Roridins-H. Helvetica Chimica Acta, 58(4): 1172~1180
Breitenstein W, Tamm C. 1978. Verrucarine and Voridine 35 Partial Synthesis of Tetrahydro verrucarin-J. Helvetica Chimica Acta, 61(6): 1975~1983
Bretz M, Beyer M, Cramer B, Knecht A, Humpf H U. 2006. Thermal degradation of the Fusarium mycotoxin deoxynivalenol. Journal of Agricultural and Food Chemistry, 54(17): 6445~6451
Capon R J, Skene C, Stewart M, Ford J, O'Hair R A J, Williams L, Lacey E, Gill J H, Heiland K, Friedel T. 2003. Aspergillicins A-E: five novel depsipeptides from the marine-derived fungus Aspergillus carneus. Organic & Biomolecular Chemistry, 1(11): 1856~1862
Chinworrungsee M, Wiyakrutta S, Sriubolmas N, Chuailua P, Suksamrarn A. 2008. Cytotoxic activities of trichothecenes isolated from an endophytic fungus belonging to order hypocreales. Archives of Pharmacal Research, 31(5): 611~616
Choi S U, Choi E J, Kim K H, Kim N Y, Kwon B M, Kim S U, Bok S H, Lee S Y, Lee C O. 1996. Cytotoxicity of trichothecenes to human solid tumor cells in vitro. Archives of Pharmacal Research, 19(1): 6~11
Desjardins A E, McCormick S P, Appell M. 2007. Structure-activity relationships of trichothecene toxins in an Arabidopsis thaliana leaf assay. Journal of Agricultural and Food Chemistry, 55(16): 6487~6492
Dorit R L W F, Barnes R D. 1991. Zoology: 1009~1011
Eppley R M, Mazzola E P, Highet R J, Bailey W J. 1977. Structure of Satratoxin H, a Metabolite of Stachybotrys-Atra - Application of Proton and C-13 Nuclear Magnetic-Resonance. Journal of Organic Chemistry, 42(2): 240~243
Faulkner D J, Harper M K, Haygood M G, Salomon C E, Schmidt E W. 2000. Symbiotic bacteria in sponges: sources of bioactive substances. Drugs from the sea: 107~119
Fetz E, Bohner B, Tamm C. 1965. Die Konstitution Von Verrucarin J. Helvetica Chimica Acta, 48(7): 1669~&
Gnanamani A, Kavitha V, Radhakrishnan N, Rajakumar G S, Sekaran G, Mandal A B. 2010. Microbial products (biosurfactant and extracellular chromate reductase) of marine microorganism are the potential agents reduce the oxidative stress induced by toxic heavy metals. Colloids and Surfaces B-Biointerfaces, 79(2): 334~339
Halliwell G. 1961. Action of Cellulolytic Enzymes from Myrothecium Verrucaria. Biochemical Journal, 79(1): 185~192
Jarvis B B, Desilva T, Mcalpine J B, Swanson S J, Whittern D N. 1992. New Trichoverroids from Myrothecium-Verrucaria Isolated by High-Speed Countercurrent Chromatography. Journal of Natural Products, 55(10): 1441~1446
Jarvis B B, Midiwo J O, Desilva T. 1981. Verrucarin-L, a New Macrocyclic Trichothecene. Journal of Antibiotics, 34(1): 120~121
Jarvis B B, Midiwo J O, Mazzola E P. 1984. Antileukemic Compounds Derived by Chemical Modification of Macrocyclic Trichothecenes .2. Derivatives of Roridin-a and Roridin-H and Verrucarin-a and Verrucarin-J. Journal of Medicinal Chemistry, 27(2): 239~244
Jarvis B B, Wang S J. 1999. Stereochemistry of the roridins. Diastereomers of roridin E. Journal of Natural Products, 62(9): 1284~1289
Jin H Z, Lee J H, Zhang W D, Lee H B, Hong Y S, Kim Y H, Lee J J. 2007. Harzianums A and B produced by a fungal strain, Hypocrea sp. F000527, and their cytotoxicity against tumor cell lines. Journal of Asian Natural Products Research, 9(3): 203~207
Kikuchi H, Miyagawa Y, Nakamura K, Sahashi Y, Inatomi S, Oshima Y. 2004a. A novel carbon skeletal trichothecane, tenuipesine A, isolated from an entomopathogenic fungus, Paecilomyces tenuipes. Organic Letters, 6(24): 4531~4533
Kikuchi H, Miyagawa Y, Sahashi Y, Inatomi S, Haganuma A, Nakahata N, Oshima Y. 2004b. Novel spirocyclic trichothecanes, spirotenuipesine A and B, isolated from entomopathogenic fungus, Paecilomyces tenuipes. Journal of Organic Chemistry, 69(2): 352~356
Kikuchi H, Miyagawa Y, Sahashi Y, Inatomi S, Haganuma A, Nakahata N, Oshima Y. 2004c. Novel trichothecanes, paecilomycine A, B, and C, isolated from entomopathogenic fungus, Paecilomyces tenuipes. Tetrahedron Letters, 45(33): 6225~6228
Konishi K, Iida A, Kaneko M, Tomioka K, Tokuda H, Nishino H, Kumeda Y. 2003. Cancer preventive potential of trichothecenes from Trichothecium roseum. Bioorganic & Medicinal Chemistry, 11(12): 2511~2518
Koyama K, Ishino M, Takatori K, Sugita T, Kinoshita K, Takahashi K. 2004. Phomactin H, a novel diterpene from an unidentified marine-derived fungus. Tetrahedron Letters, 45(37): 6947~6948
Krohn K, Steingrover K, Aust H J, Draeger S, Schulz B. 2003. Biologically active metabolites from fungi, 17. 8-alpha-acetoxyverrol, a new member of the trichothecene sesquiterpenes. Natural Product Research, 17(1): 67~70
Laurent D, Guella G, Roquebert M F, Farinole F, Mancini I, Pietra F. 2000. Cytotoxins, mycotoxins and drugs from a new deuteromycete, Acremonium neo-caledoniae, from the southwestern lagoon of New Caledonia. Planta Medica, 66(1): 63~66
Liu J Y, Huang L L, Ye Y H, Zou W X, Guo Z J, Tan R X. 2006. Antifungal and new metabolites of Myrothecium sp Z16, a fungus associated with white croaker Argyrosomus argentatus. Journal of AppliedMicrobiology, 100(1): 195~202
Madhyastha M S, Marquardt R R, Abramson D. 1994. Structure-Activity-Relationships and Interactions among Trichothecene Mycotoxins as Assessed by Yeast Bioassay. Toxicon, 32(9): 1147~1152
Meyer S W, Mordhorst T F, Lee C, Jensen P R, Fenical W, Kock M. 2010. Penilumamide, a novel lumazine peptide isolated from the marine-derived fungus, Penicillium sp CNL-338. Organic & Biomolecular Chemistry, 8(9): 2158~2163
Murakami Y, Okuda T, Shindo K. 2001. Roridin L, M and Verrucarin M, new macrocyclic trichothecene group antitumor antibiotics, from Myrothecium verrucaria. Journal of Antibiotics, 54(11): 980~983
Murao S, Tanaka N. 1981. A New Enzyme Bilirubin Oxidase Produced by Myrothecium-Verrucaria Mt-1. Agricultural and Biological Chemistry, 45(10): 2383~2384
Murao S, Tanaka N. 1982. Isolation and Identification of a Microorganism Producing Bilirubin Oxidase. Agricultural and Biological Chemistry, 46(8): 2031~2034
Muroga Y, Yamada T, Numata A, Tanaka R. 2010. 11-and 4 '-Epimers of Chaetomugilin A, Novel Cytostatic Metabolites from Marine Fish-Derived Fungus Chaetomium globosum. Helvetica Chimica Acta, 93(3): 542~549
Namikoshi M, Akano K, Meguro S, Kasuga I, Mine Y, Takahashi T, Kobayashi H. 2001. A new macrocyclic trichothecene, 12,13-deoxyroridin E, produced by the marine-derived fungus Myrothecium roridum collected in Palau. Journal of Natural Products, 64(3): 396~398
Nicholson G M. 2007. Fighting the global pest problem: Preface to the special Toxicon issue on insecticidal toxins and their potential for insect pest control. Toxicon, 49(4): 413~422
Nitao J K, Meyer S L F, Schmidt W F, Fettinger J C, Chitwood D J. 2001. Nematode-antagonistic trichothecenes from Fusarium equiseti. Journal of Chemical Ecology, 27(5): 859~869
Oclarit J M, Belarmino I B M, Ieee. 2009. Quantitative analysis of omega-3 aliphatic acid from schizochytrium sp. dzam (order thraustochytriales division chromista) under different spectral photo-emissions. Oceans 2009 - Europe, Vols 1 and 2. New York, Ieee: 5~11
Ren S, Ma W, Xu T H, Lin X P, Yin H, Yang B, Zhou X F, Yang X W, Long L J, Lee K J, Gao Q P, Liu Y H. 2010. Two novel alkaloids from the South China Sea marine sponge Dysidea sp. Journal of Antibiotics, 63(12): 699~701
Saikawa Y, Okamoto H, Inui T, Makabe M, Okuno T, Suda T, Hashimoto K, Nakata M. 2001. Toxic principles of a poisonous mushroom Podostroma cornu-damae. Tetrahedron, 57(39): 8277~8281
Schoettler S, Bascope M, Sterner O, Anke T. 2006. Isolation and characterization of two verrucarins from Myrothecium roridum. Zeitschrift Fur Naturforschung C-a Journal of Biosciences, 61(5-6): 309~314
Shen L, Jiao R H, Ye Y H, Wang X T, Xu C, Song Y C, Zhu H L, Tan R X. 2006. Absolute configuration of new cytotoxic and other bioactive trichothecene macrolides. Chemistry-a European Journal, 12(21): 5596~5602
Shen L, Wang J A S, Shen H J, Song Y C, Tan R X. 2010. A New Cytotoxic Trichothecene Macrolide from the Endophyte Myrothecium roridum. Planta Medica, 76(10): 1004~1006
Sivapathasekaran C, Das P, Mukherjee S, Saravanakumar J, Mandal M, Sen R. 2010. Marine Bacterium Derived Lipopeptides: Characterization and Cytotoxic Activity Against Cancer Cell Lines. International Journal of Peptide Research and Therapeutics, 16(4): 215~222
Stierle A C, Cardellina J H, Singleton F L. 1988. A Marine Micrococcus Produces Metabolites Ascribed to the Sponge Tedania-Ignis. Experientia, 44(11-12): 1021~1021
Sugawara T, Tanaka A, Nagai K, Suzuki K, Okada G. 1997. New members of the trichothecene family. Journal of Antibiotics, 50(9): 778~780
Sugitakonishi Y, Kumagai S, Mizuochi T. 1994. The Cytotoxicity of Macrocyclic Trichothecenes, Roridin-a and Verrucarin-a, on Murine T-Cells Is Reduced by Ia-Negative Splenic Adherent Cells. Toxicon, 32(9): 1051~1057
Suzumura K, Yokoi T, Funatsu M, Nagai K, Tanaka K, Zhang H P, Suzuki K. 2003. YM-266183 and YM-266184, novel thiopeptide antibiotics produced by Bacillus cereus isolated from a marine sponge - II. Structure elucidation. Journal of Antibiotics, 56(2): 129~134
Thompson W L, Wannemacher R W. 1986. Structure-Function-Relationships of 12,13-Epoxytrichothecene Mycotoxins in Cell-Culture-Comparison to Whole Animal Lethality. Toxicon, 24(10): 985~994
Tiepo E N, Correa A X R, Resgalla C, Cotelle S, Ferard J F, Radetski C M. 2010. Terrestrial short-term ecotoxicity of a green formicide. Ecotoxicology and Environmental Safety, 73(5): 939~943
Wagenaar M M, Clardy J. 2001a. Dicerandrols, new antibiotic and cytotoxic dimers produced by the fungus Phomopsis longicolla isolated from an endangered mint. Journal of Natural Products, 64(8): 1006~1009
Wagenaar M M, Clardy J. 2001b. Two new roridins isolated from Myrothecium sp. Journal of Antibiotics, 54(6): 517~520
Wang T, Zhang Y, Pei Y H. 2007. Two novel trichothecenes from Myrothecium roridum. Medicinal Chemistry Research, 16(4): 155~161
Wright A D, McCluskey A, Robertson M J, MacGregor K A, Gordon C P, Guenther J. 2011. Anti-malarial, anti-algal, anti-tubercular, anti-bacterial, anti-photosynthetic, and anti-fouling activity of diterpene and diterpene isonitriles from the tropical marine sponge Cymbastela hooperi. Organic & Biomolecular Chemistry, 9(2): 400~407
Wu Q X, Crews M S, Draskovic M, Sohn J, Johnson T A, Tenney K, Valeriote F A, Yao X J, Bjeldanes L F, Crews P. 2010. Azonazine, a Novel Dipeptide from a Hawaiian Marine Sediment-Derived Fungus, Aspergillus insulicola. Organic Letters, 12(20): 4458~4461
Xie L W, Jiang S M, Zhu H H, Sun W, Ouyang Y C, Dai S K, Li X. 2008. Potential inhibitors against Sclerotinia sclerotiorum, produced by the fungus Myrothecium sp associated with the marine sponge Axinella sp. European Journal of Plant Pathology, 122(4): 571~578
Xu J Z, Takasaki A, Kobayashi H, Oda T, Yamada J, Mangindaan R E P, Ukai K, Nagai H, Namikoshi M. 2006. Four new macrocyclic trichothecenes from two strains of marine-derived fungi of the genus Myrothecium. Journal of Antibiotics, 59(8): 451~455
Yu N J, Guo S X, Lu H Y. 2002. Cytotoxic macrocyclic trichothecenes from the mycelia of Calcarisporium arbuscula Preuss. Journal of Asian Natural Products Research, 4(3): 179~183
Zhang D J, Liu R F, Li Y G, Tao L M, Tian L. 2010. Two New Antifungal Cyclic Lipopeptides from Bacillus marinus B-9987. Chemical & Pharmaceutical Bulletin, 58(12): 1630~1634
Zhang Y, Wang T, Pei Y H, Hua H M, Feng B M. 2002. Aspergillin PZ, a novel isoindole-alkaloid from Aspergillus awamori. Journal of Antibiotics, 55(8): 693~695