Abstract
This report reviews biologically active secondary metabolites from marine-derived members of the fungal genus Aspergillus. Pharmacological activities and biological roles of the secondary metabolites from marine-derived Aspergillus spp. were addressed in respect of pharmaceutical potential.
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References
Afiyatullov SS, Kalinovskii AI, Pivkin MV, Dmitrenok PS, Kuznetsova TA (2005) Alkaloids from the marine isolate of the fungus Aspergillus fumigatus. Chem Natr Comp 41:236–238
Akaike H, Horie H, Kato K, Akita H (2008) Total synthesis of (+)-asperlin. Tetrahedron-Asymmetry 19:1100–1105
Aqil F, Zahin M, El Sayed KA, Ahmad I, Orabi KY, Arif JM (2011) Antimicrobial, antioxidant, and antimutagenic activities of selected marine natural products and tobacco cembranoids. Drug Chem Toxicol 34:167–179
Arif JM, Al-Hazzani AA, Kunhi M, Al-Khodairy F (2004) Novel marine compounds: Anticancer or genotoxic? J Biomed Biotechnol 2004:93–98
Asami Y, Jang JH, Soung NK, He L, Moon DO, Kim JW, Oh H, Muroi M, Osada H, Kim BY, Ahn JS (2012) Protuboxepin A, a marine fungal metabolite, inducing metaphase arrest and chromosomal misalignment in tumor cells. Bioorg Med Chem 20:3799–3806
Beck B, Hess S, Domling A (2000) One-pot synthesis and biological evaluation of aspergillamides and analogues. Bioorg Med Chem Lett 10:1701–1705
Belofsky GN, Jensen PR, Renner MK, Fenical W (1998) New cytotoxic sesquiterpenoid nitrobenzoyl esters from a marine isolate of the fungus Aspergillus versicolor. Tetrahedron 54:1715–1724
Bennett JW (2009) Aspergillus: a primer for the novice. Med Mycol 47:S5–S12
Blunden G (2001) Biologically active compounds from marine organisms. Phytother Res 15:89–94
Bugni TS, Abbanat D, Bernan VS, Maiese WM, Greenstein M, Van Wagoner RM, Ireland CM (2000) Yanuthones: novel metabolites from a marine isolate of Aspergillus niger. J Org Chem 65:7195–7200
Choi EJ, Park JS, Kim YJ, Jung JH, Lee JK, Kwon HC, Yang HO (2011) Apoptosis-inducing effect of diketopiperazine disulfides produced by Aspergillus sp. KMD 901 isolated from marine sediment on HCT116 colon cancer cell lines. J Appl Microbiol 110:304–313
Chooi Y-H, Fang J, Liu H, Filler SG, Wang P, Tang Y (2013) Genome mining of a prenylated and immunosuppressive polyketide from pathogenic fungi. Org Lett 14(18):4770–4773
Cohen E, Koch L, Thu KM, Rahamim Y, Aluma Y, Ilan M, Yarden O, Carmeli S (2011) Novel terpenoids of the fungus Aspergillus insuetus isolated from the Mediterranean sponge Psammocinia sp collected along the coast of Israel. Bioorg Med Chem 19:6587–6593
Cueto M, Jensen PR, Fenical W (2002) Aspergilloxide, a novel sesterterpene epoxide from a marine-derived fungus of the genus Aspergillus. Org Lett 4:1583–1585
Cueto M, Macmillan JB, Jensen PR, Fenical W (2006) Tropolactones A-D, four meroterpenoids from a marine-derived fungus of the genus Aspergillus. Phytochemistry 67:1826–1831
Cui CM, Li XM, Li CS, Sun HF, Gan SS, Wang BG (2009) Benzodiazepine alkaloids from marine-derived endophytic fungus Aspergillus ochraceus. Helv Chim Acta 92:1366–1370
Cui CM, Li XM, Meng L, Li CS, Huang CG, Wang BG (2010) 7-Nor-ergosterolide, a pentalactone-containing norsteroid and related steroids from the marine-derived endophytic Aspergillus ochraceus EN-31. J Nat Prod 73:1780–1784
Dang HT, Xiao B, Lee YM, Hong J, Lee CO, Choi JS, Jung JH (2012) Synthesis of Fellutamide C and its diastereomer. Bull Korean Chem Soc 33:2777–2780
Du L, Ai J, Li DH, Zhu TJ, Wang Y, Knauer M, Bruhn T, Liu HB, Geng MY, Gu QQ, Bringmann G (2011) Aspergiolides C and D: spirocyclic aromatic polyketides with potent protein kinase c-met inhibitory effects. Chem Eur J 17:1319–1326
Du L, Zhu TJ, Fang YC, Liu HB, Gu QQ, Zhu WM (2007) Aspergiolide A, a novel anthraquinone derivative with naphtho[1,2,3-de]chromene-2,7-dione skeleton isolated from a marine-derived fungus Aspergillus glaucus. Tetrahedron 63:1085–1088
Du L, Zhu TJ, Fang YC, Liu HB, Gu QQ, Zhu WM (2008) Aspergiolide A, a novel anthraquinone derivative with naphtho[1,2,3-de]chromene-2,7-dione skeleton isolated from a marine-derived fungus Aspergillus glaucus (vol 63, pg 1085, 2007). Tetrahedron 64:4657–4657
Fenical W, Jensen PR, Cheng XC (2000) Avrainvillamide, a cytotoxic marine natural products, and derivatives thereof. US19990274899 19990323.
Finefield JM, Greshock TJ, Sherman DH, Tsukamoto S, Williams RM (2011) Notoamide E: biosynthetic incorporation into notoamides C and D in cultures of Aspergillus versicolor NRRL 35600. Tetrahedron Lett 52:1987–1989
Fremlin LJ, Piggott AM, Lacey E, Capon RJ (2009) Cottoquinazoline A and cotteslosins A and B, metabolites from an Australian marine-derived strain of Aspergillus versicolor. J Nat Prod 72:666–670
Greve H, Mohamed IE, Pontius A, Kehraus S, Gross H, Konig GM (2010) Fungal metabolites: structural diversity as incentive for anticancer drug development. Phytochem Rev 9:537–545
Haefner B (2003) Drugs from the deep: marine natural products as drug candidates. Drug Discov Today 8:536–544
Hayashi Y, Orikasa S, Tanaka K, Kanoh K, Kiso Y (2000) Total synthesis of anti-microtubule diketopiperazine derivatives: phenylahistin and aurantiamine. J Org Chem 65:8402–8405
He L, Nan MH, Oh HC, Kim YH, Jang JH, Erikson RL, Ahn JS, Kim BY (2011) Asperlin induces G(2)/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells. Biochem Biophys Res Commun 409:489–493
Hines J, Groll M, Fahnestock M, Crews CM (2008) Proteasome inhibition by fellutamide B induces nerve growth factor synthesis. Chem Biol 15:501–512
Hiort J, Maksimenka K, Reichert M, Perovic-Ottstadt S, Lin WH, Wray V, Steube K, Schaumann K, Weber H, Proksch P, Ebel R, Muiller WEG, Bringmann G (2004) New natural products from the sponge-derived fungus Aspergillus niger. J Nat Prod 67:1532–1543
Holler U, Wright AD, Matthee GF, Konig GM, Draeger S, Aust HJ, Schulz B (2000) Fungi from marine sponges: diversity, biological activity and secondary metabolites. Mycol Res 104:1354–1365
Huang HB, Wang FZ, Luo MH, Chen YC, Song YX, Zhang WM, Zhang S, Ju JH (2012) Halogenated anthraquinones from the marine-derived fungus Aspergillus sp. SCSIO F063. J Nat Prod 75:1346–1352
Ingavat N, Dobereiner J, Wiyakrutta S, Mahidol C, Ruchirawat S, Kittakoop P (2009) Aspergillusol A, an alpha-glucosidase inhibitor from the marine-derived fungus Aspergillus aculeatus. J Nat Prod 72:2049–2052
Itabashi T, Nozawa K, Nakajima S, Kawai K (1993) A new azaphilone, falconensin-H, from Emericella-falconensis. Chem Pharm Bull 41:2040–2041
Kanoh K, Kohno S, Asari T, Harada T, Katada J, Muramatsu M, Kawashima H, Sekiya H, Uno I (1997) (−)-phenylahistin: a new mammalian cell cycle inhibitor produced by Aspergillus ustus. Bioorg Med Chem Lett 7:2847–2852
Kanoh K, Kohno S, Katada J, Hayashi Y, Muramatsu M, Uno I (1999) Antitumor activity of phenylahistin in vitro and in vivo. Biosci Biotechnol Biochem 63:1130–1133
Kato H, Yoshida T, Tokue T, Nojiri Y, Hirota H, Ohta T, Williams RM, Tsukamoto S (2007) Notoamides A-D: prenylated indole alkaloids isolated from a marine-derived fungus, Aspergillus sp. Angew Chem Int Ed 46:2254–2256
Kitano M, Yamada T, Amagata T, Minoura K, Tanaka R, Numata A (2012) Novel pyridino-α-pyrone sesquiterpene type pileotin produced by a sea urchin-derived Aspergillus sp. Tetrahedron Lett 53:4192–4194
Lam KS (2007) New aspects of natural products in drug discovery. Trends Microbiol 15:279–289
Lee DS, Jeong GS, Li B, Lee SU, Oh H, Kim YC (2011a) Asperlin from the marine-derived fungus Aspergillus sp SF-5044 exerts anti-inflammatory effects through heme oxygenase-1 expression in murine macrophages. J Pharm Sci 116:283–295
Lee SM, Li XF, Jiang HL, Cheng JG, Seong S, Choi HD, Son BW (2003) Terreusinone, a novel UV-A protecting dipyrroloquinone from the marine algicolous fungus Aspergillus terreus. Tetrahedron Lett 44:7707–7710
Lee SU, Asami Y, Lee D, Jang JH, Ahn JS, Oh H (2011b) Protuboxepins A and B and protubonines A and B from the marine-derived fungus Aspergillus sp SF-5044. J Nat Prod 74:1284–1287
Lee YM, Dang HT, Hong J, Lee CO, Bae KS, Kim DK, Jung JH (2010a) A cytotoxic lipopeptide from the sponge-derived fungus Aspergillus versicolor. Bull Korean Chem Soc 31:205–208
Lee YM, Dang HT, Li J, Zhang P, Hong J, Lee CO, Jung JH (2011c) A cytotoxic Fellutamide analogue from the sponge-derived fungus Aspergillus versicolor. Bull Korean Chem Soc 32:3817–3820
Lee YM, Li H, Hong J, Cho HY, Bae KS, Kim MA, Kim DK, Jung JH (2010b) Bioactive metabolites from the sponge-derived fungus Aspergillus versicolor. Arch Pharm Res 33:231–235
Li D, Xu Y, Shao C-L, Yang R-Y, Zheng C-J, Chen Y-Y, Fu X-M, Qian P-Y, She Z-G, de Voogd NJ, Wang C-Y (2012) Antibacterial bisabolane-type sesquiterpenoids from the sponge-derived fungus Aspergillus sp. Mar Drug 10:234–241
Li JL, Lee YM, Hong J, Bae KS, Choi JS, Jung JH (2011) A new antioxidants from the marine sponge-derived fungus Aspergillus versicolor. Nat Prod Sci 17:14–18
Li XF, Lee SM, Choi HD, Kang JS, Son BW (2003) Microbial transformation of terreusinone, an ultraviolet-A (UV-A) protecting dipyrroloquinone, by Streptomyces sp. Chem Pharm Bull 51:1458–1459
Li Y, Li XF, Kim SK, Kang JS, Choi HD, Rho JR, Son BW (2004) Golmaenone, a new diketopiperazine alkaloid from the marine-derived fungus Aspergillus sp. Chem Pharm Bull 52:375–376
Li Y, Li X, Son BW (2005) Antibacterial and radical scavenging epoxycyclohexenones and aromatic polyols from a marine isolate of the fungus Aspergillus. Nat Prod Sci 11:136–138
Lin G, Li DY, Chidawanyika T, Nathan C, Li HL (2010) Fellutamide B is a potent inhibitor of the Mycobacterium tuberculosis proteasome. Arch Biochem Biophys 501:214–220
Lindquist N, Fenical W, Vanduyne GD, Clardy J (1991) Isolation and structure determination of diazonamide-a and diazonamide-B, unusual cytotoxic metabolites from the marine ascidian Diazona-chinensis. J Am Chem Soc 113:2303–2304
Liu CH, Meng JC, Zou WX, Huang LL, Tang HQ, Tan RX (2002) Antifungal metabolite with a new carbon skeleton from Keissleriella sp Y54108, a marine filamentous fungus. Planta Med 68:363–365
Liu D, Li XM, Meng L, Li CS, Gao SS, Shang Z, Proksch P, Huang CG, Wang BG (2011) Nigerapyrones A–H, alpha-pyrone derivatives from the marine mangrove-derived endophytic fungus Aspergillus niger MA-132. J Nat Prod 74:1787–1791
Liu HB, Edrada-Ebel R, Ebel R, Wang Y, Schulz B, Draeger S, Muller WEG, Wray V, Lin WH, Proksch P (2009) Drimane sesquiterpenoids from the fungus Aspergillus ustus isolated from the marine sponge Suberites domuncula. J Nat Prod 72:1585–1588
Lopez-Gresa MP, Cabedo N, Gonzalez-Mas MC, Ciavatta ML, Avila C, Primo J (2009) Terretonins E and F, Inhibitors of the mitochondrial respiratory chain from the marine-derived fungus Aspergillus insuetus. J Nat Prod 72:1348–1351
Lu ZY, Wang Y, Miao CD, Liu PP, Hong K, Zhu WM (2009) Sesquiterpenoids and benzofuranoids from the marine-derived fungus Aspergillus ustus 094102. J Nat Prod 72:1761–1767
Mayer AMS, Gustafson KR (2003) Marine pharmacology in 2000: antitumor and cytotoxic compounds. Int J Cancer 105:291–299
Miao FP, Li XD, Liu XH, Cichewicz RH, Ji NY (2012) Secondary metabolites from an algicolous Aspergillus versicolor Strain. Mar Drug 10:131–139
Millward M, Mainwaring P, Mita A, Federico K, Lloyd GK, Reddinger N, Nawrocki S, Mita M, Spear MA (2012) Phase 1 study of the novel vascular disrupting agent plinabulin (NPI-2358) and docetaxel. Investig New Drugs 30:1065–1073
Namikoshi M, Negishi R, Nagai H, Dmitrenok A, Kobayashi H (2003) Three new chlorine containing antibiotics from a marine-derived fungus Aspergillus ostianus collected in Pohnpei. J Antibiot 56:755–761
Ogawa A, Murakami C, Kamisuki S, Kuriyama I, Yoshida H, Sugawara F, Mizushina Y (2004) Pseudodeflectusin, a novel isochroman derivative from Aspergillus pseudodeflectus a parasite of the sea weed, Sargassum fusiform, as a selective human cancer cytotoxin. Bioorg Med Chem Lett 14:3539–3543
Parvatkar RR, D’souza C, Tripathi A, Naik CG (2009) Aspernolides A and B, butenolides from a marine-derived fungus Aspergillus terreus. Phytochemistry 70:128–132
Proksch P, Ebel R, Edrada R, Riebe F, Liu H, Diesel A, Bayer M, Li X, Lin WH, Grebenyuk V, Mueller WEG, Draeger S, Zuccaro A, Schulz B (2008) Sponge-associated fungi and their bioactive compounds: the suberites case. Bot Mar 51:209–218
Proksch P, Ebel R, Lin WH (2006) Sponge-derived fungi—a prolific source for new natural products. Acta Pharmacol Sin 27:16–16
Proksch P, Putz A, Ortlepp S, Kjer J, Bayer M (2010) Bioactive natural products from marine sponges and fungal endophytes. Phytochem Rev 9:475–489
Qian-Cutrone JF, Huang S, Shu YZ, Vyas D, Fairchild C, Menendez A, Krampitz K, Dalterio R, Klohr SE, Gao Q (2002) Stephacidin A and B: two structurally novel, selective inhibitors of the testosterone-dependent prostate LNCaP cells. J Am Chem Soc 124:14556–14557
Qiao MF, Ji NY, Liu XH, Li K, Zhu QM, Xue QZ (2010) Indoloditerpenes from an algicolous isolate of Aspergillus oryzae. Bioorg Med Chem Lett 20:5677–5680
Rateb ME, Ebel R (2011) Secondary metabolites of fungi from marine habitats. Nat Prod Rep 28:290–344
Schneekloth JS, Sanders JL, Hines J, Crews CM (2006) Neurotrophic peptide aldehydes: solid phase synthesis of fellutamide B and a simplified analog. Bioorg Med Chem Lett 16:3855–3858
Shao CL, Wang CY, Wei MY, Gu YC, She ZG, Qian PY, Lin YC (2011) Aspergilones A and B, two benzylazaphilones with an unprecedented carbon skeleton from the gorgonian-derived fungus Aspergillus sp. Bioorg Med Chem Lett 21:690–693
Shearer CA, Descals E, Kohlmeyer B, Kohlmeyer J, Marvanova L, Padgett D, Porter D, Raja HA, Schmit JP, Thorton HA, Voglymayr H (2007) Fungal biodiversity in aquatic habitats. Biodivers Conserv 16:49–67
Shigemori H, Wakuri S, Yazawa K, Nakamura T, Sasaki T, Kobayashi J (1991) Fellutamide-a and fellutamide-B, cytotoxic peptides from a marine fish-possessing fungus Penicillium-Fellutanum. Tetrahedron 47:8529–8534
Song F, Liu X, Guo H, Ren B, Chen C, Piggott AM, Yu K, Gao H, Wang Q, Liu M, Liu X, Dai H, Zhang L, Capon RJ (2012) Brevianamides with antitubercular potential from a amrine-derived isolate of Aspergillus versicolor. Org Lett 14(18):4770–4773
Su S, Kakeya H, Osada H, Porco JA (2003) Synthesis and cell cycle inhibition of the peptide enamide natural products terpeptin and the aspergillamides. Tetrahedron 59:8931–8946
Sugiyama Y, Yoshida K, Abe N, Hirota A (2010) Soybean lipoxygenase inhibitory and DPPH radical-scavenging activities of aspernolide A and butyrolactones I and II. Biosci Biotechnol Biochem 74:881–883
Sun LL, Shao CL, Chen JF, Guo ZY, Fu XM, Chen M, Chen YY, Li R, De Voogd NJ, She ZG, Lin YC, Wang CY (2012) New bisabolane sesquiterpenoids from a marine-derived fungus Aspergillus sp isolated from the sponge Xestospongia testudinaria. Bioorg Med Chem Lett 22:1326–1329
Tao KK, Du L, Sun XQ, Cai MH, Zhu TJ, Zhou XS, Gu QQ, Zhang YX (2009) Biosynthesis of aspergiolide A, a novel antitumor compound by a marine-derived fungus Aspergillus glaucus via the polyketide pathway. Tetrahedron Lett 50:1082–1085
Toske SG, Jensen PR, Kauffman CA, Fenical W (1998) Aspergillamides A and B: modified cytotoxic tripeptides produced by a marine fungus of the genus Aspergillus. Tetrahedron 54:13459–13466
Tsuda M, Mugishima T, Komatsu K, Sone T, Tanaka M, Mikami Y, Shiro M, Hirai M, Ohizumi Y, Kobayashi J (2003) Speradine A, a new pentacyclic oxindole alkaloid from a marine-derived fungus Aspergillus tamarii. Tetrahedron 59:3227–3230
Tsukamoto S, Hirota H, Imachi M, Fujimuro M, Onuki H, Ohta T, Yokosawa H (2005) Himeic acid A: a new ubiquitin-activating enzyme inhibitor isolated from a marine-derived fungus, Aspergillus sp. Bioorg Med Chem Lett 15:191–194
Tsukamoto S, Kato H, Samizo M, Nojiri Y, Onuki H, Hirota H, Ohta T (2008) Notoamides F-K, prenylated indole alkaloids isolated from a marine-derived Aspergillus sp. J Nat Prod 71:2064–2067
Ui H, Shiomi K, Yamaguchi Y, Masuma R, Nagamitsu T, Takano D, Sunazuka T, Namikoshi M, Omura S (2001) Nafuredin, a novel inhibitor of NADH-fumarate reductase, produced by Aspergillus niger FT-0554. J Antibiot 54:234–238
Von Nussbaum F (2003) Stephacidin B—a new stage of complexity within prenylated indole alkaloids from fungi. Angew Chem Int Ed 42:3068–3071
Wang F, Fang YC, Zhu TJ, Zhang M, Lin AQ, G QQ, Zhu WM (2008) Seven new prenylated indole diketopiperazine alkaloids from holothurian-derived fungus Aspergillus fumigatus. Tetrahedron 64:7986–7991
Wang X, You J, King JB, Powell DR, Cichewicz RH (2012a) Waikialoid A suppresses hyphal morphogenesis and inhibits biofilm development in pathogenic Candida albicans. J Nat Prod 75:707–715
Wang Y, Li ZL, Bai J, Zhang LM, Wu X, Zhang L, Pei YH, Jing YK, Hua HM (2012b) 2,5-Diketopiperazines from the marine-derived fungus Aspergillus fumigatus YK-7. Chem Biol 9:385–393
Wang Y, Zheng J, Liu P, Wang W, Zhu W (2011) three new compounds from Aspergillus terreus PT067-2 grown in a high salt medium. Mar Drug 9:1368–1378
Wu QX, Crews MS, Draskovic M, Sohn J, Johnson TA, Tenney K, Valeriote FA, Yao XJ, Bjeldanes LF, Crews P (2010) Azonazine, a novel dipeptide from a Hawaiian marine sediment-derived fungus, Aspergillus insulicola. Org Lett 12:4458–4461
Yamada T, Imai E, Nakatuji K, Numata A, Tanaka R (2007) Cephalimysin A, a potent cytotoxic metabolite from an Aspergillus species separated from a marine fish. Tetrahedron Lett 48:6294–6296
Yamazaki Y, Tanaka K, Nicholson B, Deyanat-Yazdi G, Potts B, Yoshida T, Oda A, Kitagawa T, Orikasa S, Kiso Y, Yasui H, Akamatsu M, Chinen T, Usui T, Shinozaki Y, Yakushiji F, Miller BR, Neuteboom S, Palladino M, Kanoh K, Lloyd GK, Hayashi Y (2012) Synthesis and structure-activity relationship study of antimicrotubule agents phenylahistin derivatives with a didehydropiperazine-2,5-dione structure. J Med Chem 55:1056–1071
Zhang YP, Ling S, Fang YC, Zhu TJ, Gu QQ, Zhu WM (2008) Isolation, structure elucidation, and antimycobacterial properties of dimeric naphtho-gamma-pyrones from the marine-derived fungus Aspergillus carbonarius. Chem Biol 5:93–100
Zhao WY, Zhu TJ, Fan GT, Liu HB, Fang YC, Gu QQ, Zhu WM (2010) Three new dioxopiperazine metabolites from a marine-derived fungus Aspergillus fumigatus Fres. Nat Prod Res 24:953–957
Zheng JK, Zhu HJ, Hong K, Wang Y, Liu PP, Wang X, Peng XP, Zhu WM (2009) Novel cyclic hexapeptides from marine-derived fungus, Aspergillus sclerotiorum PT06-1. Org Lett 11:5262–5265
Zhou YM, Mandi A, Debbab A, Wray V, Schulz B, Muller WEG, Lin WH, Proksch P, Kurtan T, Aly AH (2011) New austalides from the sponge-associated fungus Aspergillus sp. Eur J Org Chem 2011:6009–6019
Zhuang YB, Teng XC, Wang Y, Liu PP, Wan H, Li GQ, Zhu WM (2011) Cyclopeptides and polyketides from coral-associated fungus, Aspergillus versicolor LCJ-5-4. Tetrahedron 67:7085–7089
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This study was supported by the Korea Research Foundation (grant nos. 20110013721 and 20090083538)
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Lee, Y.M., Kim, M.J., Li, H. et al. Marine-Derived Aspergillus Species as a Source of Bioactive Secondary Metabolites. Mar Biotechnol 15, 499–519 (2013). https://doi.org/10.1007/s10126-013-9506-3
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DOI: https://doi.org/10.1007/s10126-013-9506-3