海洋真菌Alternaria alternate YX-25和放线菌Streptomyces exfoliates YX-32共培养的次级代谢产物研究
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摘要
目的研究来源于福建云霄红树林底泥中的链格孢霉属真菌AlternariaalternateYX-25和链霉菌属放线菌Streptomyces exfoliatus YX-32共培养产生的次级代谢产物。方法通过硅胶柱色谱、Sephadex LH-20凝胶柱色谱以及半制备HPLC等色谱技术对共培养所产生的次级代谢产物进行分离纯化。采用MS和NMR等波谱方法及文献对比鉴定化合物的结构。结果从2株共培养的发酵产物中分离得到9个化合物,分别鉴定为gliotoxin(1)、12,13-dihydroxy-fumitremorgin C(2)、fumitremorgin(3)、bisdethiobis (methylthio) gliotoxin(4)、demethoxyfumitremorgin C(5)、vermistatin(6)、cyclo-(L-Trp-L-Pro)(7)、6-methoxyspirotryprostatin B(8)和citrinolactone D(9)。结论首次从海洋真菌Alternaria alternate YX-25和放线菌Streptomyces exfoliatus YX-32共培养发酵产物中发现了9个化合物,为吲哚二酮哌嗪类、聚酮类、环肽类化合物。共培养方法可使代谢产物丰富,可作为一种诱导次级代谢产物的新方法。
Objective To study the secondary metabolites of the co-culture of fungus Alternaria alternata YX-25 and Streptomycesexfoliatus YX-32 isolated from mangrove mud in Yunxiao Country of Fujian Province. Methods The compounds were purified by silica gel and Sephadex LH-20, followed by semi-preparative chromatography. The structures of the compounds were determined by MS and NMR. Results Nine compounds were isolated from the crude extract, which were identified as gliotoxin(1), 12,13-dihydroxy-fumitremorgin C(2), fumitremorgin(3), bisdethiobis(methylthio)gliotoxin(4), demethoxyfumitremorgin C(5), vermistatin(6), cyclo-(L-Trp-L-Pro)(7), 6-methoxyspirotryprostatin B(8), and citrinolactone D(9). Conclusion Nine compounds were isolated for the first time from co-culture of the fungus Alternaria alternata YX-25 and Streptomyces exfoliates YX-32, including indole diketopiperazines, polyketides, and cyclopeptides. The co-cultivation method can be as a new method for enrichment of secondary metabolites.
Objective To study the secondary metabolites of the co-culture of fungus Alternaria alternata YX-25 and Streptomycesexfoliatus YX-32 isolated from mangrove mud in Yunxiao Country of Fujian Province. Methods The compounds were purified by silica gel and Sephadex LH-20, followed by semi-preparative chromatography. The structures of the compounds were determined by MS and NMR. Results Nine compounds were isolated from the crude extract, which were identified as gliotoxin(1), 12,13-dihydroxy-fumitremorgin C(2), fumitremorgin(3), bisdethiobis(methylthio)gliotoxin(4), demethoxyfumitremorgin C(5), vermistatin(6), cyclo-(L-Trp-L-Pro)(7), 6-methoxyspirotryprostatin B(8), and citrinolactone D(9). Conclusion Nine compounds were isolated for the first time from co-culture of the fungus Alternaria alternata YX-25 and Streptomyces exfoliates YX-32, including indole diketopiperazines, polyketides, and cyclopeptides. The co-cultivation method can be as a new method for enrichment of secondary metabolites.
引文
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[2]李越中,陈琦.海洋微生物资源及其产生生物活性代谢产物的研究[J].生物工程进展,2000,20(5):28-31.
[3]Shu Y Z.Recent natural products based drug development:A pharmaceutical industry perspective[J].JNat Prod,1998,61(8):1053-1071.
[4]Pettit R K.Mixed fermentation for natural product drug discovery[J].Appl Microbiol Biot,2009,83(1):19-25.
[5]Yu L Y,Hu Z F,Ma Z J.Production of bioactive tryptamine derivatives by co-culture of marine Streptomyces with Bacillus mycoides[J].Nat Prod Res,2015,29(22):2087-2091.
[6]Wang Y,Wang L P,Zhuang Y B,et al.Phenolic polyketides from the co-cultivation of marine-derived Penicillium sp.WC-29-5 and Streptomyces fradiae 007[J].Mar Drugs,2014,12(4):2079-2088.
[7]Nguyen V T,Lee J S,Qian Z J,et al.Gliotoxin isolated from marine fungus Aspergillus sp.induces apoptosis of human cervical cancer and chondrosarcoma cells[J].Mar Drugs,2013,12(1):69-87.
[8]Abraham W R,Arfmann H A.12,13-Dihydroxyfumitremorgin C from Aspergillus fumigatus[J].Phytochemistry,1990,29(3):1025-1026.
[9]Cui C B,Kakeya H,Osada H.Novel mammalian cell cycle inhibitors,tryprostatins A,B,and other diketopiperazines produced by Aspergillus fumigatus.Part 2.Physico-chemical properties and structures[J].Cheminformation,2010,27(47):534-540.
[10]Afiyatullov S S,Kalinovskii A I,Pivkin M V,et al.Alkaloids from the marine isolate of the fungus Aspergillus fumigatus[J].Chem Nat Compd,2005,41(2):236-238.
[11]Fuska J,Uhrín D,Proksa B,et al.The structure of vermistatin,a new metabolite from Penicillium vermiculatum[J].J Antibiot,1986,39(11):1605-1608.
[12]Li X,Dobretsov S,Xu Y,et al.Antifouling diketopiperazines produced by a deep-sea bacterium,Streptomyces fungicidicus[J].Biofouling,2006,22(3):201-208.
[13]Zhang M,Wang W L,Fang Y C,et al.Cytotoxic alkaloids and antibiotic nordammarane triterpenoids from the marine-derived fungus Aspergillus sydowi[J].J Nat Prod,2008,71(6):985-989.
[14]Wang M L,Lu C H,Xu Q Y,et al.Four new citrinin derivatives from a marine-derived Penicillium sp.fungal strain[J].Molecules,2013,18(5):5723-5734.
[15]Zheng C J,Park S H,Koshino H,et al.Verticillin G,a new antibacterial compound from Bionectra byssicola[J].J Antibiot,2007,60(1):61-64.
[16]Kuramochi K,Ohnishi K,Fujieda S,et al.Synthesis and biological activities of neoechinulin A derivatives:New aspects of structure-activity relationships for neoechinulin A[J].Chem Pharm Bull,2008,56(12):1738-1743.
[17]Wang F,Fang Y,Zhu T,et al.Seven new prenylated indole diketopiperazine alkaloids from holothurianderived fungus Aspergillus fumigatus[J].Tetrahedron,2008,64(34):7986-7991.
[18]Li G Y,Yang T,Luo Y G,et al.Brevianamide J,a new indole alkaloid dimer from fungus Aspergillus versicolor[J].Org Lett,2009,11(16):3714-3717.
[19]刘少斌,王延亮,张庆林,等.埃博霉素异源表达研究进展[J].军事医学,2009,33(1):84-87.
[20]Jamie H,Kilian G,Dyason K,et al.The effect of the isomers of cyclo-(Trp-Pro)on heart and ion-channel activity[J].J Pharm Pharmacol,2002,54(12):1659-1665.