海绵共附生系状菌中生物活性物质的研究
摘要
本文以稻瘟霉(Pyricularia oryzae)分生孢子和菌丝形态变异或生长抑制为指标，从海绵共附生系状菌的发酵产物中筛选具有抗真菌和抗肿瘤等生物活性的物质。通过对100株海绵来源的系状真菌的发酵液进行抗稻瘟霉活性筛选，得到9株具有良好抗稻瘟霉活性且稳定的菌株。采用代谢产物的提取分离和活性检测同步进行的方法，对活性最好的菌株，即05JANF163／165、05JANF151、05JANF154、05ABR145、05ABR116、98F152和S_(1-1)，进行了大量发酵，从其发酵液中共分离得到20个化合物，根据理化性质和各种波谱学等方法鉴定了19个单体化合物的结构，分别为Fusarielin A(1)、Fusarielin B(2)、Fusarielin E(3)、(-)-Oxysporidinone(4)、Roridin A(5)、Roridin H(6)、Roridin J(7)、Verrucarin A(8)、Verrucarin B(9)、Verrucarin L Acetate(10)、Verrucarin J(11)、Deoxyfusapyrone(12)、5′-Hydroxyzearalenol(13)、Zearalenol (14)、Zearalenone(15)、8′-Hydroxyzearalenone(16)、Zeaenone(17)、α，β-Dehydrocurvularin(18)、MycophenolicAcid(19)。其中化合物(3)和(13)为新的天然产物，并首次得到了化合物(6)和(7)的X-射线单晶衍射的立体结构。
化合物(1)和(3)能使稻瘟霉分生孢子发生严重变形或使菌丝生长发生弯曲变形，最小抑制浓度均为3.1μg／mL；化合物(5)、(6)、(9)和(11)能使稻瘟霉菌丝发生弱卷曲变形，它们的最小抑制浓度分别为12.5μg／mL、3.1μg／mL、0.2μg／mL和0.2μg／mL；化合物(12)能使稻瘟霉菌丝发生弱卷曲强串珠状变形，其最小抑制浓度为3.1μg／mL；化合物(4)、(7)、(8)、(10)、(15)、(17)、(18)和(19)抑制稻瘟霉菌丝生长的最小抑制浓度分别为25μg／mL、6.2μg／mL、1.6μg／mL、0.2μg／mL、3.1μg／mL、0.1μg／mL、25μg／mL和25μg／mL。利用稻瘟霉生物活性模型筛选出的这些生物活性化合物同文献中报道的有关它们的其它生物活性试验结果有很好的一致性，这也说明该生物模型能够有效的指导海洋生物活性物质的分离纯化，是一个适用的初筛体系。
Bioactive substances that interfere with microtubule function can generally inhibit the conidia growth of Pyricularia oryzae (a plant pathogenic fungus) and induce morphological deformation of conidia or mycelia of Pyricularia oryzae by swelling, curling, beads formation and hyper-divergence effect. We apply the method using conidia of Pyricularia oryzae as a primary screening assay for compounds such as antifungal antibiotics and anticancer substances from secondary metabolites of sponge-associated fungi. From 100 fungi samples isolated from sponges, we obtained 9 strains possessing better and stable activity. From the fermentation broth of strain 05JANF163/165, 05JANF151, 05JANF154, 05ABR145, 05ABR116, 98F152 and S_(1-1) , twenty active compounds were isolated and purified by activity-guided fractionation. Structures of nineteen compounds were established on the basis of various NMR spectroscopic analyses, including 1D-and 2D-NMR spectroscopic analyses (~1H-~1H COSY, ROESY, HMQC, and HMBC spectra), and MS (FAB, EI and ESI). The nineteen compounds were Fusarielin A (1) , Fusarielin B (2) , Fusarielin E (3) , (-)-Oxysporidinone (4) , Roridin A (5) , Roridin H (6) , Roridin J (7) , Verrucarin A (8) , Verrucarin B (9) , Verrucarin L Acetate (10) , Verrucarin J (11) , Deoxyfusapyrone (12) , 5'-Hydroxyzearalenol (13) , Zearalenol (14) , 8'-Hydroxyzearalenone (15) , Zearalenone(16) , Zeaenone (17) ,α,β-Dehydrocurvularin (18) and Mycophenolic Acid (19) . Compounds (3) and (13) were new nature compounds, and compounds (6) and (7) were first elucidated their spectroscopic structures by X-ray single-crystal analysis.
Compounds (1) and (3) inhibited the conidia growth of Pyricularia oryzae by swelling effect and induced morphological changes of the mycelia by curling effect with the minimum inhibitory concentration (MIC) 3．1μg/mL. Compounds (5) , (6) , (9) and (11) induced morphological changes of the mycelia by weak curling effect with MIC 12．5μg/mL, 3．1 μg/mL, 0．2μg/mL and 0．2μg/mL, respectively. Compound (12) induced morphological changes of the mycelia by weak curling and strong beads formation with MIC 3．1μg/mL. Compounds (4) , (7) , (8) , (10) , (15) , (17) , (18) and (19) inhibited the mycelia growth with MIC 25μg/mL, 6．2μg/mL, 1．6μg/mL, 0．2μg/mL, 3．1μg/mL, 0．1μg/mL, 25μg/mL and 25μg/mL, respectively.
The activity results of our study accorded with the relevant reports and it showed that the bioassay method using conidia of Pyricularia oryzae could efficiently guide the isolation of the bioactive metabolites of marine-derived fungi and could be a primary screening for bioactive substances.
化合物(1)和(3)能使稻瘟霉分生孢子发生严重变形或使菌丝生长发生弯曲变形，最小抑制浓度均为3.1μg／mL；化合物(5)、(6)、(9)和(11)能使稻瘟霉菌丝发生弱卷曲变形，它们的最小抑制浓度分别为12.5μg／mL、3.1μg／mL、0.2μg／mL和0.2μg／mL；化合物(12)能使稻瘟霉菌丝发生弱卷曲强串珠状变形，其最小抑制浓度为3.1μg／mL；化合物(4)、(7)、(8)、(10)、(15)、(17)、(18)和(19)抑制稻瘟霉菌丝生长的最小抑制浓度分别为25μg／mL、6.2μg／mL、1.6μg／mL、0.2μg／mL、3.1μg／mL、0.1μg／mL、25μg／mL和25μg／mL。利用稻瘟霉生物活性模型筛选出的这些生物活性化合物同文献中报道的有关它们的其它生物活性试验结果有很好的一致性，这也说明该生物模型能够有效的指导海洋生物活性物质的分离纯化，是一个适用的初筛体系。
Bioactive substances that interfere with microtubule function can generally inhibit the conidia growth of Pyricularia oryzae (a plant pathogenic fungus) and induce morphological deformation of conidia or mycelia of Pyricularia oryzae by swelling, curling, beads formation and hyper-divergence effect. We apply the method using conidia of Pyricularia oryzae as a primary screening assay for compounds such as antifungal antibiotics and anticancer substances from secondary metabolites of sponge-associated fungi. From 100 fungi samples isolated from sponges, we obtained 9 strains possessing better and stable activity. From the fermentation broth of strain 05JANF163/165, 05JANF151, 05JANF154, 05ABR145, 05ABR116, 98F152 and S_(1-1) , twenty active compounds were isolated and purified by activity-guided fractionation. Structures of nineteen compounds were established on the basis of various NMR spectroscopic analyses, including 1D-and 2D-NMR spectroscopic analyses (~1H-~1H COSY, ROESY, HMQC, and HMBC spectra), and MS (FAB, EI and ESI). The nineteen compounds were Fusarielin A (1) , Fusarielin B (2) , Fusarielin E (3) , (-)-Oxysporidinone (4) , Roridin A (5) , Roridin H (6) , Roridin J (7) , Verrucarin A (8) , Verrucarin B (9) , Verrucarin L Acetate (10) , Verrucarin J (11) , Deoxyfusapyrone (12) , 5'-Hydroxyzearalenol (13) , Zearalenol (14) , 8'-Hydroxyzearalenone (15) , Zearalenone(16) , Zeaenone (17) ,α,β-Dehydrocurvularin (18) and Mycophenolic Acid (19) . Compounds (3) and (13) were new nature compounds, and compounds (6) and (7) were first elucidated their spectroscopic structures by X-ray single-crystal analysis.
Compounds (1) and (3) inhibited the conidia growth of Pyricularia oryzae by swelling effect and induced morphological changes of the mycelia by curling effect with the minimum inhibitory concentration (MIC) 3．1μg/mL. Compounds (5) , (6) , (9) and (11) induced morphological changes of the mycelia by weak curling effect with MIC 12．5μg/mL, 3．1 μg/mL, 0．2μg/mL and 0．2μg/mL, respectively. Compound (12) induced morphological changes of the mycelia by weak curling and strong beads formation with MIC 3．1μg/mL. Compounds (4) , (7) , (8) , (10) , (15) , (17) , (18) and (19) inhibited the mycelia growth with MIC 25μg/mL, 6．2μg/mL, 1．6μg/mL, 0．2μg/mL, 3．1μg/mL, 0．1μg/mL, 25μg/mL and 25μg/mL, respectively.
The activity results of our study accorded with the relevant reports and it showed that the bioassay method using conidia of Pyricularia oryzae could efficiently guide the isolation of the bioactive metabolites of marine-derived fungi and could be a primary screening for bioactive substances.
引文
[1] 李光友，刘发义，海洋生物活性物质的研究与开发．海洋开发与管理．1998，(2)，45-50
[2] 刘志鸿，程力，牟海津，海洋微生物活性物质的研究概况．中国水产科学，1999，6(4)，99-103
[3] 黄建设，龙丽娟，海洋天然产物及其生理活性的研究进展．海洋通报，2001，20(4)，83-91
[4] 黄美珍，李志棠，海洋药物研究开发趋势．福建水产，2006，(3)，80-83
[5] P. Proksch, R. A. Edrada, R. Ebel, Drugs from the seas-current status and microbiological implications. Appl Microbiol Biotechnol, 2002, 59, 125-134
[6] Jensen P R, Fenical W. Strategies for the discovery of secondary metabolites from marine bacteria: Ecological perspectives. Annu. Rev. Microbiol. 1994, 48, 559-584
[7] D. John Faulkner, Marine natural products. Nat. Prod. Rep., 1998, 15, 113-158
[8] D. John Faulkner, Marine natural products. Nat. Prod. Rep., 2000, 17, 7-55
[9] 徐任生 主编，天然产物化学(第二版)，科学出版社，723
[10] Vacelet J, Danadey D, Electron microscope study of the association between some sponges and bacteria. Biol. Ecol., 1977, 30, 301-314.
[11] Wilkinson C R, Microbial associations in sponges. Ecology, physiology and microbial populations of coral reef. Mar. Biol., 1978, 49, 161 167.
[12] Richmond D V, Effect of toxicants on the morphology and ring structure of fungi. Appl Microbiol, 1975, 19, 289-319.
[13] Gunji S, Arima K, Beppu T, Screening of antifungal antibiotics according to activities inducing morphological abnormalities. Agr. Biol. Chem, 1983, 47, (9), 2061-2069
[14] David J F, Kim D B, David C, et al. A whole-cell Canadida albicans assay for the detection of inhibitor towards fungal cell wall synthesis andassembly. J Antibiot, 1995, 48 (4), 306-310
[15] Sakamoto K S, Izumi M, Miyachi, A new assay method for immunosuppressants with a tacrolims (FK 506)-like mode of action. J Antibiot, 1995, 48 (7), 727-729
[16] Takahashi M, Iwasaki S, Kobayashi H, et al. Studies on macrocyclic lacton antibiotics Ⅺ, antimitotic and anti-tubulin activity of new antitumor antibiotics, rhizoxins and its homologues J. Antibiotics 1987, 40, 60-72
[17] Kobayashi H, Namikoshi M, Yoshimoto T. et al. A screening method for antimitic and antifungal substance using conidia of pyricularia oryzae, modification and application to tropical marine fungi J. Antibiotics 1996, 49 (9), 873-879
[18] Sekita S, Yoshihira K, Natori S, et al. Chem. Pharm. Bull. 1982, 30,1609-1617
[19] Kobayashi H, Sunaga G, Fudhata K, et al. Isolation and structure of an antifungal antibiotic Fusarielin A, and related compounds produced by a Fusarium sp. J Antibiotics 1995, 48(1), 42-52
[20] Lalith Jayasinghe, Hamed K. Abbas, Melissa R. Jacob, Wimal H. M. W. Herath, N. P. Dhammika Nanayakkara. N-Methyl-4-hydroxy-2-pyridinone Analogues from Fusarium oxysporum, J. Nat. Prod. 2006, 69, 439-442
[21] Jens Breinholt, Svend Ludvigsen, Birgitte R. Rassing, Connie N. Rosendahl. Oxysporidinone: A Novel, Antifungal N-Methyl-4-hydroxy-2-pyridone from Fusarium oxysporum. J. Nat. Prod. 1997, 60, 33-35
[22] B. B. Jarvis, J.O.Midiwo, J. Nat. Prod. 1982, 45, 440-448.
[23] T. Amagata, C. Rath, J. F. Rigot, N. Tarlov, K. Tenney, F.A. Valeriote, P. Crews, J. Med. Chem. 2003, 46, 4342-4350.
[24] Namikoshi M, Akano K, Meguro S, Kasuga I, Mine Y, Takahashi Y, Kobayashi H, J. Nat. Prod. 2001, 64, 396-398.
[25] Murakami Y, Okuda T, Shindo K, J. Antibiot. 2001, 54, 980-983.
[26] Alvi KA, Rabenstein J, Woodard J, Baker DD, Bergthold JD, Lynch J, Lieu KL, Braude IA, J. Nat. Prod. 2002, 65, 742-744.
[27] Jinzhong Xu, Azusa Takasaki, Hisayoshi Kobayashi, Taiko Oda, Junko Yamada, Remy E.P. Manindaan, Kazuyo Ukai, Hiroshi Nagai, Michio Namikoshi, J. Antibiot. 2006, 59,451-455.
[28] H.K. Abbas, B.B. Johnson, W.T. Shier, H. Tak, B.B. Jarvis, C.D. Boyette, Phytochemistry. 2002, 59, 309-313.
[29] Kobayashi M, Sato I, Abe F, Nitta K, Hashimoto M, Fujie A, Hino M, Hori Y, J. Antibiot. 2004, 57, 788-796.
[30] M. Isaka, J. Punya, Y. Lertwerawat, M. Tanticharoen, Y. Thebtaranonth, J. Nat. Prod. 1999, 62, 329-331.
[31] B. B. Jarvis, S. J. Wang, J. Nat. Prod. 1999,62, 1284 - 1289.
[32] Kobayashi. H., M. Namikoshi, T Yoshimoto, T.Yokochi, J.Antibiot. 1996,49, 873-879.
[33] W. Breitenstein, C. Tamm, Helv. Chim. Acta. 1975, 58,1172-1180.
[34] B.B. Jarvis, G.P. Stahly, G. Pavanasasivam, J.O. Midiwo, T. DeSilva, C.E. Holmlund, E.P. Mazzola, R.F. Geoghegan Jr., J. Org. Chem. 1982, 47, 1117-1124.
[35] B. B. Jarvis, J.O. Midiwo, E. P. Mazzola, J. Med. Chem. 1984,27, 239-244.
[36] B. B. Jarvis, J.O. Midiwo, T. DeSilva, J.Antibiot. 1981, 34, 120-122.
[37] Wagenaar MM, Clardy J, J.Antibiot. 2001, 54, 517-520.
[38] B. B. Jarvis, G.P. Stahly, G. Pavanasasivam, J.Antibiot. 1980, 33, 256-258.
[39] Li Shen, Rui H. Jiao, Yong H. Ye, Xiao T. Wang, Chen Xu, Yong C. Song, Hai L. Zhu, Ren X. Tan. Chem. Eur. J. 2006, 12,5596 - 5602
[40] Michio Namikoshi, Kyoko Akano, Shiori Meguro, Isao Kasuga, Yuji Mine, Takenori Takahashi, Hisayoshi Kobayashi. J. Nat. Prod. 2001, 64, 396-398
[41] Bruce B. Jarvis, Jacob. Midiwo, Eugene P. Mazzolat, Antileukemic Compounds Derived by Chemical Modification of Macrocyclic Trichothecenes. 2. Derivatives of Roridins A and H and Verrucarins A and J. J. Med. Chem. 1984,27, 239-244
[42] Bruce B. Jarvis, G. Patrick Stahly, Gowsala Pavanasasivam, Antileukemic Compounds Derived from the Chemical Modification of Macrocyclic Trichothecenes. 1. Derivatives of Verrucarin A, J. Med. Chem. 1980,23, 1054-1058
[43] Atsumi Shimada, Sumiyo Takeuchi, Miyako Kusano, Shozo Fujioka, Yasuo Kimura, Roridin A and verrucarin A, inhibitors of pollen development in Arabidopsis thaliana, produced by Cylindrocarpon sp. Plant Science. 2004, 166, 1307-1312
[44] Gutzwiller J, Tamm C, On the structure of verrucarine B. Verrucarine and Roridine. Helvetica chimica acta. 1965,48,177-182.
[45] Jarvis B B, Stahly G P, Pavanasasivam G, Mazzola E P, Antileukemic compounds derived from the chemical modification of macrocyclic trichothecenes. 1. Derivatives of verrucarin A. Journal of medicinal chemistry. 1980, 23(9), 1054-8.
[46] Haerri E, Loeffler W, Sigg H P, Staehelin H, Stoll Ch, Tamm Ch, Wiesinger D, On the verrucarins and roridins, a group of highly cytostatically active antibiotics from Myrothecium species. Helvetica Chimica Acta, 1962,45, 839-53.
[47] Roush, William R, Blizzard, Timothy A, Synthesis of verrucarin B. Journal of Organic Chemistry, 1984, 49(23), 4332-9.
[48] Evidente A, Amalfitano C, Pengue R, Altomare C, Highperformance liquid chromatography for the analysis of fusapyrone and deoxyfusapyrone, two antifungal α -pyrones from fusarium semitectum. Nat. Toxins. 1999, 7, 133-137
[49] Michael G. Organ, Junquan Wang, The Synthesis of Deoxyfusapyrone. 1 .An Approach to the Pyrone Moiety. J. Org. Chem. 2002, 67, 7847-7851
[50] Claudio Altomare, Giancarlo Perrone, Maria Chiara Zonno, Antonio Evidente, Raffaele Pengue, Franco Fanti, Luciano Polonelli, Biological Characterization of Fusapyrone and Deoxyfusapyrone, Two Bioactive Secondary Metabolites of Fusarium semitectum. J. Nat. Prod. 2000,63,1131-1135
[51]Claudio Altomare, Raffaele Pengue, Mara Favlla, Antonio Evidente, Angelo Visconti, StructureActivity Relationships of Derivatives of Fusapyrone, an Antifungal Metabolite of Fusarium semitectum. J. Agric. Food Chem. 2004, 52,2997-3001
[52] Saleh H. El-Sharkawy, Yusuf J. Abul-Hajj, Microbial transformation of zearalenone.2. reduction, hydroxylation, and methylation products. J. Org. Chem. 1988, 53, 515-519
[53] W. H. Urry, H. L. Wehrmeister, E. B. Hodge, P. H. Hidy, The structure of zearalenone. Tetrahedron Letters. 1966,27,3109-3114
[54] Annie Zhao, Seok H. Lee, Marina Mojena, Rosalind G. Jenkins, Denis R. Patrick, Hans E. Huber, Michael A. Goetz, Otto D. Hensens, Deborah L. Zink, Resorcylic acid lactones: naturally occurring potent and selective inhibitors of MEK. The Journal of antibiotics. 1999, 52(12), 1086-1094
[55] Fumio Sugawara, Kun-Woo Kim, Kimiko Kobayashi, Jun Uzawa, Shigeo Yoshida, Noboru Murofushi, Nobutaka Takahashi, Gary A. Strobel, Zearalenone derivatives produced by the fungus Drechslera portulacae. Phytochemistry, 1992, 31(6), 1987-1990
[56] Kobayashi A, Hino T, Yata S, Itoh T, Sato H, Kawazu K, Agric. Biol. Chem. 1988, 52, 3119-3123
[57] Robeson D J, Strobel G A, Strange R N, J. Nat. Prod. 1985,48,139-141.
[58] Hyeon S B, Ozaki A, Suzuki A, Tamura S, Agric. Biol. Chem. 1976,40, 1663-1664.
[59] Ghisalberti, E. L.; Rowland, C. Y. J. Nat. Prod. 1993, 56,2175-2177.
[60] Abdellah Zinedine, Jose Miguel Soriano, Juan Carlos Molto, Jordi Man, Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone: An oestrogenic mycotoxin. Yaoquan Liu, Zhe Li and John C. Vederas
[61] Yaoquan Liu, Zhe Li, John C. Vederas, Biosynthetic incorporation of advanced precursors into dehydrocurvularin, a polyketide phytotoxin from Alternaria cinerariae. Tetrahedron. 1998, 54, 15937-15958
[62] Adrian Covarrubias-Zuniga, Armando Gonzalez-Lucas, A total synthesis of mycophenolic acid. Tetrahedron Letters, 39(19), 2881-2882
[63] Magali Mondin, Violaine Moreau, Elisabeth Genot, Christian Combe, Jean Ripoche and Isabelle Dubus, Alterations in cytoskeletal protein expression by mycophenolic acid in human mesangial cells. Biochemical Pharmacology, 2007, 73(9), 1491-1498
[64] Scot D. Henry, Herold J. Metselaar, Richard C.B. Lonsdale, Alice Kok, Bart L. Haagmans, Hugo W. Tilanus and Luc J.W. van der Laan, Mycophenolic Acid Inhibits Hepatitis C Virus Replication and Acts in Synergy With Cyclosporin A and Interferon-a. Gastroenterology, 2006, 131(), 1452-1462
[65] Chunxiao Ying, Richard Colonno, Erik De Clercq and Johan Neyts, Ribavirin and mycophenolic acid markedly potentiate the anti-hepatitis B virus activity of entecavir. Antiviral Research, 2007, 73(3), 192-196
[66] Gyula Vegso, Anna Sebestyen, Sandor Paku, Gabor Barna, Melinda Hajdu, Maria Toth, Jeno Jaray and Laszlo Kopper, Antiproliferative and apoptotic effects of mycophenolic acid in human B-cell non-Hodgkin lymphomas. Leukemia Research, In Press, Available online 22 February 2007
[1] Goodell B, Jellison J, Liu J, Daniel G, Paszczynski A, Fekete F, et al. Low molecular weight chelators and phenolic compounds isolated from wood decay fungi and their role in the fungal biodegradation of wood. J Biotechnol. 1997, 53, 133-62
[2] Enoki A, Hirano T, Tanaka H. Extracellular substance from the brown-rot basidiomycete Gloeophyllum trabeum that produces and reduces hydrogen peroxide. Mater Organismen. 1992, 27, 247-61
[3] Hider RC. Siderophore mediated absorption of iron. Struct Bond. 1984, 58, 25-87
[4] Winkelmann G. Microbial siderophores-mediated transport. Biochem Soc Trans. 2002,30, 691-6
[5] Tanaka H, Itakura S, Enoki A. Hydroxyl radical generation by an extracellular low-molecular-weight substance and phenol oxidase activity during wood degradation by the white-rot basidiomycete Trametes versicolor. J Biotechnol. 1999, 74, 57-70
[6] Valdeir Arantes, Adriane M.F. Milagres, Evaluation of different carbon sources for production of iron-reducing compounds by Wolfiporia cocos and Perenniporia medulla-panis. Process Biochemistry. 2006, 41, 887-891
[7] Isil Seyis, Nilufer Aksoz, Effect of carbon and nitrogen sources on xylanase production by Trichoderma harzianum 1073 D3. International Biodeterioration & Biodegradation. 2005, 55, 115-119
[8] Ing-Lung Shih, Bi-Wen Chou, Chien-Cheng Chen, Jane-Yii Wu, Chienyan Hsieh, Study of mycelial growth and bioactive polysaccharide production in batch and fed-batch culture of Grifola frondosa. Bioresource Technology. 2007, available online at ScienceDirect
[9] Wice, B.M., Reitzer, L.J., Kennell, D., The continuous growth of vertebrate cells in the absence of sugar. J. Biol. Chem. 1981, 256,7812-7819
[10] Pellerin, L., Magistretti, P.J., Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proceedings of the National Academy of Sciences USA. 1994,91,10625-10629
[11] Certik, M., Megova, J., Horenitzky, R., Effect of nitrogen sources on the activities of lipogenic enzymes in oleaginous fungus Cunninghamella echinulata. J. Appl. Microbiol. 1999,45, 289-293
[12] L.J. Yu, W.M. Qin, W.Z. Lan, P.P. Zhou, M. Zhu, Improved arachidonic acids production from the fungus Mortierella alpina by glutamate supplementation. Bioresource Technology, 2003, 88, 265-268
[13] Andarwulan, N., Shetty, K., Improvement of pea (Pisum sativum) seed vigour response by fish protein hydrolysates in combination with acetyl salicylic acid. Proc. Biochem. 1999, 5, 159-165
[14] Veridiana Lenartovicz, Cristina Giatti Marques de Souza, Fabiana Guillen Moreira, Rosane Marina Peralta, Temperature and carbon source affect the production and secretion of a thermostable β -xylosidase by Aspergillus fumigatus. Process Biochemistry.2003, 38, 1775-1780
[15] San-Lang Wanga, Tsu-Chau Yieh, Ing-Lung Shih, Production of antifungal compounds by Pseudomonas aeruginosa K-187 using shrimp and crab shell powder as a carbon source. Enzyme and Microbial Technology. 1999,25, 142-148
[16] Vania Battestin, Gabriela Alves Macedo, Tannase production by Paecilomyces variotii. Bioresource Technology, 2007, 98, 1832 - 1837
[17] Y. Marlida, N. Saari, Z. Hassan, K. Muhammad, J. Bakar, S. Radu. Production of raw sago starch degrading enzyme from selected endophytic fungi. Proceedings of the 10th National Biotechnology Seminar. Malaysia 1998, 349-353.
[18] Yetti Marlida, Nazamid Saarib, Zaiton Hassan, Son Radu, Improvement in raw sago starch degrading enzyme production from Acremonium sp. endophytic fungus using carbon and nitrogen sources. Enzyme and Microbial Technology. 2000, 27, 511-515
[19] Zeng Xiaobo, Wang haiying, He Linyu, Lin Yongcheng, Li Zhongtao, Medium optimization of carbon and nitrogen sources for the production of eucalyptene A and xyloketal A from Xylaria sp. 2508 using response surface methodology. Process Biochemistry, 2006, 41,293-298
[20] Yerra Koteswara Rao, Kuen-Juh Tsay, Wen-Shi Wu, Yew-Min Tzeng, Medium optimization of carbon and nitrogen sources for the production of spores from Bacillus amyloliquefaciens B128 using response surface methodology. Process Biochemistry. 2007, 42, 535-541
[21] 陈贵斌，张建勇，牛晋阳，郑卉，元英进，胡宗定．高校化学工程学报．2003，17(5)，521-526
[22] Kim, M. H., Kong, Y.J., Back, H., Hyun, H.H., 2005. Purification and characterization of micrococcin GO5, a bacteriocin produced by Micrococcus sp. GO5 isolated from kimchi. J. Food Prot. 68, 157-163.
[23] Mi-Hee Kim, Yoon-Jung Kong, Hong Baek, Hyung-Hwan Hyun, Optimization of culture conditions and medium composition for the production of micrococcin GO5 by Micrococcus sp. GO5. Journal of Biotechnology. 2006, 121, 54-61
[24] 康源，王永红，庄英萍，储炬，张嗣良．Mn~(2+)对必特螺旋霉素产生菌代谢和必特螺旋霉素合成的影响．微生物学报．2005，45(1)，81-85
[25] Sandra D. Dyal, Laziz Bouzidi, Suresh S. Narine, Maximizing the production of c-linolenic acid in Mortierella ramanniana var. ramanniana as a function of pH, temperature and carbon source, nitrogen source, metal ions and oil supplementation. Food Research International, 2005, 38, 815-829
[26] 吴健，戴桂馥，李宗伟，袁天阳，张广乐，霍裕平．铁离子对庆大霉素高产菌株发酵产量的抑制及解除．河南工业大学学报(自然科学版)．2005，26(3)，37-40
[27] 潘劲松，潘波，王力，万中义．增加无机盐和表面活性剂对B-3543摇瓶发酵的影响．湖北农业科学，2000，NO．3，45-46
[28] 林明，任南琪，王爱杰，张颖，王相晶，马放，几种金属离子对高效产氢细菌产氢能力的促进作用．哈尔滨工业大学学报．2003，35(2)，147-151
[29] 周华，潘自皓，高振，韦萍，万红贵，营养因子对大肠杆菌发酵产转氨酶的影响．食品与发酵工业．2006，32(7)，1-4
[30] Mehmet Inan, Vijay Chiruvolu, Kent M. Eskridge, George P. Vlasuk, Kenneth Dickerson, Scott Brown, and Michael M. Meagher, Optimization of temperature-glycerol -pH conditions for a fed-batch fermentation process for recombinant hookworm (Ancylostoma caninum ) anticoagulant peptide AcAP-5 production by Pichia pastoris. Enzyme and Microbial Technology, 1999, 24, 438-445
[31] Clark RB, Zeto SK., Growth and root colonization of mycotrldzal maize grown on acid and alkaline soil. Soil Biology and Biochemistry. 1996, 28(10/11), 1505-1511
[32] Clark RB. Zeto SK., Mineral acquisition by mycordfizal maize grown on acid and alkaline soil. So il Biology and Biochemistry. 1996, 28(10/11), 1495-1503
[33] Clark RB., Zero SK., Zobel RW., Arbuscular mycorrhizal fungal isolate efectiveness on growth and root colonization of Panicum virgatum inacidic soil. Soil Biology and Biochemistry. 1999, 31, 1757-1763
[34] 朱红惠，姚青，pH值对Gigaspora margarita孢子萌发、菌丝生长与聚磷酸盐含量的影响，菌物学报2006，25(1)，120-124
[35] 陈剑锋，陈浩，张元兴，郭养浩，pH值和温度对西索米星发酵的影响．药物生物技术．2006，13(3)， 223-226
[36] Yuan-Shuai Liu, Jian-Yong Wu, Kwok-ping Ho, Characterization of oxygen transfer conditions and their effects on Phaffia rhodozyma growth and carotenoid production in shake-flask cultures. Biochemical Engineering Journal. 2006, 27, 331-335
[37] 王岁楼，吴晓宗，王琼波，李国富，孙君社，溶氧对几种真菌漆酶发酵的影响．精细化工．2006，23(1)， 32-34
[38] 吉国栋，周波，高红亮，常忠义，杨俊．溶氧浓度对微生物谷氨酰胺转胺酶发酵的影响．西北农林科技大学学报(自然科学版)．2006，34(1)，75-78
[39] Carsten Baumchen, Amd Knoll, Bemward Husemann, Juri Seletzky, Bemd Maier, Carsten Dietrich, Ghassem Amoabediny, Jochen Buchs, Effect of elevated dissolved carbon dioxide concentrations on growth of Corynebacterium glutamicum on D-glucose and L-lactate. Journal of Biotechnology, 2007, 128, 868-874
[40] Adinarayana K, Prabhakar T, Srinivasulu V, et al. Optimization of process parameters for cephalosporin C production under solid state fermentation from Acremonium chrysogenum[J]. Process Biochem, 2003, 39(2), 171-177
[41] Venkatesw Arlu Gk, Murali Krishna P S, Ashok Pandey, et al. Evaluation of Amycolatopsis mediterranei VA 18 for production of rifamycin-B. Process Biochem, 2000, 36(4), 305-309
[42] Adinarayana K, Ellaiah P, Srivivasulu B, et al. Response surface methodological approach to optimize the nutritional parameters for neomycin production by Streptomyces marinensis under solid state fermentation[J]. Process Bioehem, 2003, 38(11), 1565-1572.
[2] 刘志鸿，程力，牟海津，海洋微生物活性物质的研究概况．中国水产科学，1999，6(4)，99-103
[3] 黄建设，龙丽娟，海洋天然产物及其生理活性的研究进展．海洋通报，2001，20(4)，83-91
[4] 黄美珍，李志棠，海洋药物研究开发趋势．福建水产，2006，(3)，80-83
[5] P. Proksch, R. A. Edrada, R. Ebel, Drugs from the seas-current status and microbiological implications. Appl Microbiol Biotechnol, 2002, 59, 125-134
[6] Jensen P R, Fenical W. Strategies for the discovery of secondary metabolites from marine bacteria: Ecological perspectives. Annu. Rev. Microbiol. 1994, 48, 559-584
[7] D. John Faulkner, Marine natural products. Nat. Prod. Rep., 1998, 15, 113-158
[8] D. John Faulkner, Marine natural products. Nat. Prod. Rep., 2000, 17, 7-55
[9] 徐任生 主编，天然产物化学(第二版)，科学出版社，723
[10] Vacelet J, Danadey D, Electron microscope study of the association between some sponges and bacteria. Biol. Ecol., 1977, 30, 301-314.
[11] Wilkinson C R, Microbial associations in sponges. Ecology, physiology and microbial populations of coral reef. Mar. Biol., 1978, 49, 161 167.
[12] Richmond D V, Effect of toxicants on the morphology and ring structure of fungi. Appl Microbiol, 1975, 19, 289-319.
[13] Gunji S, Arima K, Beppu T, Screening of antifungal antibiotics according to activities inducing morphological abnormalities. Agr. Biol. Chem, 1983, 47, (9), 2061-2069
[14] David J F, Kim D B, David C, et al. A whole-cell Canadida albicans assay for the detection of inhibitor towards fungal cell wall synthesis andassembly. J Antibiot, 1995, 48 (4), 306-310
[15] Sakamoto K S, Izumi M, Miyachi, A new assay method for immunosuppressants with a tacrolims (FK 506)-like mode of action. J Antibiot, 1995, 48 (7), 727-729
[16] Takahashi M, Iwasaki S, Kobayashi H, et al. Studies on macrocyclic lacton antibiotics Ⅺ, antimitotic and anti-tubulin activity of new antitumor antibiotics, rhizoxins and its homologues J. Antibiotics 1987, 40, 60-72
[17] Kobayashi H, Namikoshi M, Yoshimoto T. et al. A screening method for antimitic and antifungal substance using conidia of pyricularia oryzae, modification and application to tropical marine fungi J. Antibiotics 1996, 49 (9), 873-879
[18] Sekita S, Yoshihira K, Natori S, et al. Chem. Pharm. Bull. 1982, 30,1609-1617
[19] Kobayashi H, Sunaga G, Fudhata K, et al. Isolation and structure of an antifungal antibiotic Fusarielin A, and related compounds produced by a Fusarium sp. J Antibiotics 1995, 48(1), 42-52
[20] Lalith Jayasinghe, Hamed K. Abbas, Melissa R. Jacob, Wimal H. M. W. Herath, N. P. Dhammika Nanayakkara. N-Methyl-4-hydroxy-2-pyridinone Analogues from Fusarium oxysporum, J. Nat. Prod. 2006, 69, 439-442
[21] Jens Breinholt, Svend Ludvigsen, Birgitte R. Rassing, Connie N. Rosendahl. Oxysporidinone: A Novel, Antifungal N-Methyl-4-hydroxy-2-pyridone from Fusarium oxysporum. J. Nat. Prod. 1997, 60, 33-35
[22] B. B. Jarvis, J.O.Midiwo, J. Nat. Prod. 1982, 45, 440-448.
[23] T. Amagata, C. Rath, J. F. Rigot, N. Tarlov, K. Tenney, F.A. Valeriote, P. Crews, J. Med. Chem. 2003, 46, 4342-4350.
[24] Namikoshi M, Akano K, Meguro S, Kasuga I, Mine Y, Takahashi Y, Kobayashi H, J. Nat. Prod. 2001, 64, 396-398.
[25] Murakami Y, Okuda T, Shindo K, J. Antibiot. 2001, 54, 980-983.
[26] Alvi KA, Rabenstein J, Woodard J, Baker DD, Bergthold JD, Lynch J, Lieu KL, Braude IA, J. Nat. Prod. 2002, 65, 742-744.
[27] Jinzhong Xu, Azusa Takasaki, Hisayoshi Kobayashi, Taiko Oda, Junko Yamada, Remy E.P. Manindaan, Kazuyo Ukai, Hiroshi Nagai, Michio Namikoshi, J. Antibiot. 2006, 59,451-455.
[28] H.K. Abbas, B.B. Johnson, W.T. Shier, H. Tak, B.B. Jarvis, C.D. Boyette, Phytochemistry. 2002, 59, 309-313.
[29] Kobayashi M, Sato I, Abe F, Nitta K, Hashimoto M, Fujie A, Hino M, Hori Y, J. Antibiot. 2004, 57, 788-796.
[30] M. Isaka, J. Punya, Y. Lertwerawat, M. Tanticharoen, Y. Thebtaranonth, J. Nat. Prod. 1999, 62, 329-331.
[31] B. B. Jarvis, S. J. Wang, J. Nat. Prod. 1999,62, 1284 - 1289.
[32] Kobayashi. H., M. Namikoshi, T Yoshimoto, T.Yokochi, J.Antibiot. 1996,49, 873-879.
[33] W. Breitenstein, C. Tamm, Helv. Chim. Acta. 1975, 58,1172-1180.
[34] B.B. Jarvis, G.P. Stahly, G. Pavanasasivam, J.O. Midiwo, T. DeSilva, C.E. Holmlund, E.P. Mazzola, R.F. Geoghegan Jr., J. Org. Chem. 1982, 47, 1117-1124.
[35] B. B. Jarvis, J.O. Midiwo, E. P. Mazzola, J. Med. Chem. 1984,27, 239-244.
[36] B. B. Jarvis, J.O. Midiwo, T. DeSilva, J.Antibiot. 1981, 34, 120-122.
[37] Wagenaar MM, Clardy J, J.Antibiot. 2001, 54, 517-520.
[38] B. B. Jarvis, G.P. Stahly, G. Pavanasasivam, J.Antibiot. 1980, 33, 256-258.
[39] Li Shen, Rui H. Jiao, Yong H. Ye, Xiao T. Wang, Chen Xu, Yong C. Song, Hai L. Zhu, Ren X. Tan. Chem. Eur. J. 2006, 12,5596 - 5602
[40] Michio Namikoshi, Kyoko Akano, Shiori Meguro, Isao Kasuga, Yuji Mine, Takenori Takahashi, Hisayoshi Kobayashi. J. Nat. Prod. 2001, 64, 396-398
[41] Bruce B. Jarvis, Jacob. Midiwo, Eugene P. Mazzolat, Antileukemic Compounds Derived by Chemical Modification of Macrocyclic Trichothecenes. 2. Derivatives of Roridins A and H and Verrucarins A and J. J. Med. Chem. 1984,27, 239-244
[42] Bruce B. Jarvis, G. Patrick Stahly, Gowsala Pavanasasivam, Antileukemic Compounds Derived from the Chemical Modification of Macrocyclic Trichothecenes. 1. Derivatives of Verrucarin A, J. Med. Chem. 1980,23, 1054-1058
[43] Atsumi Shimada, Sumiyo Takeuchi, Miyako Kusano, Shozo Fujioka, Yasuo Kimura, Roridin A and verrucarin A, inhibitors of pollen development in Arabidopsis thaliana, produced by Cylindrocarpon sp. Plant Science. 2004, 166, 1307-1312
[44] Gutzwiller J, Tamm C, On the structure of verrucarine B. Verrucarine and Roridine. Helvetica chimica acta. 1965,48,177-182.
[45] Jarvis B B, Stahly G P, Pavanasasivam G, Mazzola E P, Antileukemic compounds derived from the chemical modification of macrocyclic trichothecenes. 1. Derivatives of verrucarin A. Journal of medicinal chemistry. 1980, 23(9), 1054-8.
[46] Haerri E, Loeffler W, Sigg H P, Staehelin H, Stoll Ch, Tamm Ch, Wiesinger D, On the verrucarins and roridins, a group of highly cytostatically active antibiotics from Myrothecium species. Helvetica Chimica Acta, 1962,45, 839-53.
[47] Roush, William R, Blizzard, Timothy A, Synthesis of verrucarin B. Journal of Organic Chemistry, 1984, 49(23), 4332-9.
[48] Evidente A, Amalfitano C, Pengue R, Altomare C, Highperformance liquid chromatography for the analysis of fusapyrone and deoxyfusapyrone, two antifungal α -pyrones from fusarium semitectum. Nat. Toxins. 1999, 7, 133-137
[49] Michael G. Organ, Junquan Wang, The Synthesis of Deoxyfusapyrone. 1 .An Approach to the Pyrone Moiety. J. Org. Chem. 2002, 67, 7847-7851
[50] Claudio Altomare, Giancarlo Perrone, Maria Chiara Zonno, Antonio Evidente, Raffaele Pengue, Franco Fanti, Luciano Polonelli, Biological Characterization of Fusapyrone and Deoxyfusapyrone, Two Bioactive Secondary Metabolites of Fusarium semitectum. J. Nat. Prod. 2000,63,1131-1135
[51]Claudio Altomare, Raffaele Pengue, Mara Favlla, Antonio Evidente, Angelo Visconti, StructureActivity Relationships of Derivatives of Fusapyrone, an Antifungal Metabolite of Fusarium semitectum. J. Agric. Food Chem. 2004, 52,2997-3001
[52] Saleh H. El-Sharkawy, Yusuf J. Abul-Hajj, Microbial transformation of zearalenone.2. reduction, hydroxylation, and methylation products. J. Org. Chem. 1988, 53, 515-519
[53] W. H. Urry, H. L. Wehrmeister, E. B. Hodge, P. H. Hidy, The structure of zearalenone. Tetrahedron Letters. 1966,27,3109-3114
[54] Annie Zhao, Seok H. Lee, Marina Mojena, Rosalind G. Jenkins, Denis R. Patrick, Hans E. Huber, Michael A. Goetz, Otto D. Hensens, Deborah L. Zink, Resorcylic acid lactones: naturally occurring potent and selective inhibitors of MEK. The Journal of antibiotics. 1999, 52(12), 1086-1094
[55] Fumio Sugawara, Kun-Woo Kim, Kimiko Kobayashi, Jun Uzawa, Shigeo Yoshida, Noboru Murofushi, Nobutaka Takahashi, Gary A. Strobel, Zearalenone derivatives produced by the fungus Drechslera portulacae. Phytochemistry, 1992, 31(6), 1987-1990
[56] Kobayashi A, Hino T, Yata S, Itoh T, Sato H, Kawazu K, Agric. Biol. Chem. 1988, 52, 3119-3123
[57] Robeson D J, Strobel G A, Strange R N, J. Nat. Prod. 1985,48,139-141.
[58] Hyeon S B, Ozaki A, Suzuki A, Tamura S, Agric. Biol. Chem. 1976,40, 1663-1664.
[59] Ghisalberti, E. L.; Rowland, C. Y. J. Nat. Prod. 1993, 56,2175-2177.
[60] Abdellah Zinedine, Jose Miguel Soriano, Juan Carlos Molto, Jordi Man, Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone: An oestrogenic mycotoxin. Yaoquan Liu, Zhe Li and John C. Vederas
[61] Yaoquan Liu, Zhe Li, John C. Vederas, Biosynthetic incorporation of advanced precursors into dehydrocurvularin, a polyketide phytotoxin from Alternaria cinerariae. Tetrahedron. 1998, 54, 15937-15958
[62] Adrian Covarrubias-Zuniga, Armando Gonzalez-Lucas, A total synthesis of mycophenolic acid. Tetrahedron Letters, 39(19), 2881-2882
[63] Magali Mondin, Violaine Moreau, Elisabeth Genot, Christian Combe, Jean Ripoche and Isabelle Dubus, Alterations in cytoskeletal protein expression by mycophenolic acid in human mesangial cells. Biochemical Pharmacology, 2007, 73(9), 1491-1498
[64] Scot D. Henry, Herold J. Metselaar, Richard C.B. Lonsdale, Alice Kok, Bart L. Haagmans, Hugo W. Tilanus and Luc J.W. van der Laan, Mycophenolic Acid Inhibits Hepatitis C Virus Replication and Acts in Synergy With Cyclosporin A and Interferon-a. Gastroenterology, 2006, 131(), 1452-1462
[65] Chunxiao Ying, Richard Colonno, Erik De Clercq and Johan Neyts, Ribavirin and mycophenolic acid markedly potentiate the anti-hepatitis B virus activity of entecavir. Antiviral Research, 2007, 73(3), 192-196
[66] Gyula Vegso, Anna Sebestyen, Sandor Paku, Gabor Barna, Melinda Hajdu, Maria Toth, Jeno Jaray and Laszlo Kopper, Antiproliferative and apoptotic effects of mycophenolic acid in human B-cell non-Hodgkin lymphomas. Leukemia Research, In Press, Available online 22 February 2007
[1] Goodell B, Jellison J, Liu J, Daniel G, Paszczynski A, Fekete F, et al. Low molecular weight chelators and phenolic compounds isolated from wood decay fungi and their role in the fungal biodegradation of wood. J Biotechnol. 1997, 53, 133-62
[2] Enoki A, Hirano T, Tanaka H. Extracellular substance from the brown-rot basidiomycete Gloeophyllum trabeum that produces and reduces hydrogen peroxide. Mater Organismen. 1992, 27, 247-61
[3] Hider RC. Siderophore mediated absorption of iron. Struct Bond. 1984, 58, 25-87
[4] Winkelmann G. Microbial siderophores-mediated transport. Biochem Soc Trans. 2002,30, 691-6
[5] Tanaka H, Itakura S, Enoki A. Hydroxyl radical generation by an extracellular low-molecular-weight substance and phenol oxidase activity during wood degradation by the white-rot basidiomycete Trametes versicolor. J Biotechnol. 1999, 74, 57-70
[6] Valdeir Arantes, Adriane M.F. Milagres, Evaluation of different carbon sources for production of iron-reducing compounds by Wolfiporia cocos and Perenniporia medulla-panis. Process Biochemistry. 2006, 41, 887-891
[7] Isil Seyis, Nilufer Aksoz, Effect of carbon and nitrogen sources on xylanase production by Trichoderma harzianum 1073 D3. International Biodeterioration & Biodegradation. 2005, 55, 115-119
[8] Ing-Lung Shih, Bi-Wen Chou, Chien-Cheng Chen, Jane-Yii Wu, Chienyan Hsieh, Study of mycelial growth and bioactive polysaccharide production in batch and fed-batch culture of Grifola frondosa. Bioresource Technology. 2007, available online at ScienceDirect
[9] Wice, B.M., Reitzer, L.J., Kennell, D., The continuous growth of vertebrate cells in the absence of sugar. J. Biol. Chem. 1981, 256,7812-7819
[10] Pellerin, L., Magistretti, P.J., Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proceedings of the National Academy of Sciences USA. 1994,91,10625-10629
[11] Certik, M., Megova, J., Horenitzky, R., Effect of nitrogen sources on the activities of lipogenic enzymes in oleaginous fungus Cunninghamella echinulata. J. Appl. Microbiol. 1999,45, 289-293
[12] L.J. Yu, W.M. Qin, W.Z. Lan, P.P. Zhou, M. Zhu, Improved arachidonic acids production from the fungus Mortierella alpina by glutamate supplementation. Bioresource Technology, 2003, 88, 265-268
[13] Andarwulan, N., Shetty, K., Improvement of pea (Pisum sativum) seed vigour response by fish protein hydrolysates in combination with acetyl salicylic acid. Proc. Biochem. 1999, 5, 159-165
[14] Veridiana Lenartovicz, Cristina Giatti Marques de Souza, Fabiana Guillen Moreira, Rosane Marina Peralta, Temperature and carbon source affect the production and secretion of a thermostable β -xylosidase by Aspergillus fumigatus. Process Biochemistry.2003, 38, 1775-1780
[15] San-Lang Wanga, Tsu-Chau Yieh, Ing-Lung Shih, Production of antifungal compounds by Pseudomonas aeruginosa K-187 using shrimp and crab shell powder as a carbon source. Enzyme and Microbial Technology. 1999,25, 142-148
[16] Vania Battestin, Gabriela Alves Macedo, Tannase production by Paecilomyces variotii. Bioresource Technology, 2007, 98, 1832 - 1837
[17] Y. Marlida, N. Saari, Z. Hassan, K. Muhammad, J. Bakar, S. Radu. Production of raw sago starch degrading enzyme from selected endophytic fungi. Proceedings of the 10th National Biotechnology Seminar. Malaysia 1998, 349-353.
[18] Yetti Marlida, Nazamid Saarib, Zaiton Hassan, Son Radu, Improvement in raw sago starch degrading enzyme production from Acremonium sp. endophytic fungus using carbon and nitrogen sources. Enzyme and Microbial Technology. 2000, 27, 511-515
[19] Zeng Xiaobo, Wang haiying, He Linyu, Lin Yongcheng, Li Zhongtao, Medium optimization of carbon and nitrogen sources for the production of eucalyptene A and xyloketal A from Xylaria sp. 2508 using response surface methodology. Process Biochemistry, 2006, 41,293-298
[20] Yerra Koteswara Rao, Kuen-Juh Tsay, Wen-Shi Wu, Yew-Min Tzeng, Medium optimization of carbon and nitrogen sources for the production of spores from Bacillus amyloliquefaciens B128 using response surface methodology. Process Biochemistry. 2007, 42, 535-541
[21] 陈贵斌，张建勇，牛晋阳，郑卉，元英进，胡宗定．高校化学工程学报．2003，17(5)，521-526
[22] Kim, M. H., Kong, Y.J., Back, H., Hyun, H.H., 2005. Purification and characterization of micrococcin GO5, a bacteriocin produced by Micrococcus sp. GO5 isolated from kimchi. J. Food Prot. 68, 157-163.
[23] Mi-Hee Kim, Yoon-Jung Kong, Hong Baek, Hyung-Hwan Hyun, Optimization of culture conditions and medium composition for the production of micrococcin GO5 by Micrococcus sp. GO5. Journal of Biotechnology. 2006, 121, 54-61
[24] 康源，王永红，庄英萍，储炬，张嗣良．Mn~(2+)对必特螺旋霉素产生菌代谢和必特螺旋霉素合成的影响．微生物学报．2005，45(1)，81-85
[25] Sandra D. Dyal, Laziz Bouzidi, Suresh S. Narine, Maximizing the production of c-linolenic acid in Mortierella ramanniana var. ramanniana as a function of pH, temperature and carbon source, nitrogen source, metal ions and oil supplementation. Food Research International, 2005, 38, 815-829
[26] 吴健，戴桂馥，李宗伟，袁天阳，张广乐，霍裕平．铁离子对庆大霉素高产菌株发酵产量的抑制及解除．河南工业大学学报(自然科学版)．2005，26(3)，37-40
[27] 潘劲松，潘波，王力，万中义．增加无机盐和表面活性剂对B-3543摇瓶发酵的影响．湖北农业科学，2000，NO．3，45-46
[28] 林明，任南琪，王爱杰，张颖，王相晶，马放，几种金属离子对高效产氢细菌产氢能力的促进作用．哈尔滨工业大学学报．2003，35(2)，147-151
[29] 周华，潘自皓，高振，韦萍，万红贵，营养因子对大肠杆菌发酵产转氨酶的影响．食品与发酵工业．2006，32(7)，1-4
[30] Mehmet Inan, Vijay Chiruvolu, Kent M. Eskridge, George P. Vlasuk, Kenneth Dickerson, Scott Brown, and Michael M. Meagher, Optimization of temperature-glycerol -pH conditions for a fed-batch fermentation process for recombinant hookworm (Ancylostoma caninum ) anticoagulant peptide AcAP-5 production by Pichia pastoris. Enzyme and Microbial Technology, 1999, 24, 438-445
[31] Clark RB, Zeto SK., Growth and root colonization of mycotrldzal maize grown on acid and alkaline soil. Soil Biology and Biochemistry. 1996, 28(10/11), 1505-1511
[32] Clark RB. Zeto SK., Mineral acquisition by mycordfizal maize grown on acid and alkaline soil. So il Biology and Biochemistry. 1996, 28(10/11), 1495-1503
[33] Clark RB., Zero SK., Zobel RW., Arbuscular mycorrhizal fungal isolate efectiveness on growth and root colonization of Panicum virgatum inacidic soil. Soil Biology and Biochemistry. 1999, 31, 1757-1763
[34] 朱红惠，姚青，pH值对Gigaspora margarita孢子萌发、菌丝生长与聚磷酸盐含量的影响，菌物学报2006，25(1)，120-124
[35] 陈剑锋，陈浩，张元兴，郭养浩，pH值和温度对西索米星发酵的影响．药物生物技术．2006，13(3)， 223-226
[36] Yuan-Shuai Liu, Jian-Yong Wu, Kwok-ping Ho, Characterization of oxygen transfer conditions and their effects on Phaffia rhodozyma growth and carotenoid production in shake-flask cultures. Biochemical Engineering Journal. 2006, 27, 331-335
[37] 王岁楼，吴晓宗，王琼波，李国富，孙君社，溶氧对几种真菌漆酶发酵的影响．精细化工．2006，23(1)， 32-34
[38] 吉国栋，周波，高红亮，常忠义，杨俊．溶氧浓度对微生物谷氨酰胺转胺酶发酵的影响．西北农林科技大学学报(自然科学版)．2006，34(1)，75-78
[39] Carsten Baumchen, Amd Knoll, Bemward Husemann, Juri Seletzky, Bemd Maier, Carsten Dietrich, Ghassem Amoabediny, Jochen Buchs, Effect of elevated dissolved carbon dioxide concentrations on growth of Corynebacterium glutamicum on D-glucose and L-lactate. Journal of Biotechnology, 2007, 128, 868-874
[40] Adinarayana K, Prabhakar T, Srinivasulu V, et al. Optimization of process parameters for cephalosporin C production under solid state fermentation from Acremonium chrysogenum[J]. Process Biochem, 2003, 39(2), 171-177
[41] Venkatesw Arlu Gk, Murali Krishna P S, Ashok Pandey, et al. Evaluation of Amycolatopsis mediterranei VA 18 for production of rifamycin-B. Process Biochem, 2000, 36(4), 305-309
[42] Adinarayana K, Ellaiah P, Srivivasulu B, et al. Response surface methodological approach to optimize the nutritional parameters for neomycin production by Streptomyces marinensis under solid state fermentation[J]. Process Bioehem, 2003, 38(11), 1565-1572.