Folia Microbiologica

, Volume 60, Issue 3, pp 259–267 | Cite as

A highly diverse spectrum of naphthoquinone derivatives produced by the endophytic fungus Biatriospora sp. CCF 4378

  • Eva Stodůlková
  • Petr Man
  • Marek Kuzma
  • Jan Černý
  • Ivana Císařová
  • Alena Kubátová
  • Milada Chudíčková
  • Miroslav Kolařík
  • Miroslav Flieger


A strain of Biatriospora sp. CCF 4378 was tested for the production of secondary metabolites under submerged fermentation conditions. Eleven compounds were isolated from the culture broth, and the structures of these compounds were determined using HRMS, NMR and X-ray analysis. In addition to six known naphthoquinone derivatives, i.e. ascomycone A, ascomycone B, 6-deoxyfusarubine, 6-deoxyanhydrofusarubine, herbarine and balticol A, one derivative of 2-azaanthraquinone, 6-deoxybostrycoidine, was also identified. Four new natural pyranonaphthoquinones were found, and these natural products were pleorubrin A, pleorubrin B, pleorubrin C and pleorubrin D. The toxicity on human cell lines of the crude naphthoquinone fraction and pure 6-deoxybostrycoidin, ascomycone B, pleorubrin B and 6-deoxyfusarubin was tested. Ascomycone B and 6-deoxyfusarubin elicited rapid cytotoxicity at micromolar concentrations.


Endophytic Fungus HMBC Correlation Naphthoquinone Derivative Submerged Fermentation Condition Ulmus Laevis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Dimethyl sulfoxide


Electrospray Ionisation


Heteronuclear multiple-bond correlation


High-performance liquid chromatography


High-resolution mass spectrometry


Internal transcribed spacer


Laser desorption/ionisation


Large-subunit ribosomal DNA


Nuclear magnetic resonance


Phosphate-buffered saline


Small-subunit ribosomal DNA



This work was supported by the LD-COST CZ project LD13039, Czech Science Foundation project No. 13-16565S, Long-Term Research Plans of the Ministry of Education, Youth and Sports of the Czech Republic No. MSM0021620858, and Charles University projects UNCE 204013/2012. Access to instrumental and other facilities was also supported by the EU (Operational Program Prague–Competitiveness project CZ.2.16/3.1.00/24023) and by the IMIC institutional research concept RVO61388971.

Supplementary material

12223_2014_366_MOESM1_ESM.docx (170 kb)
ESM 1 (DOCX 170 kb)


  1. Altschul SF, Madden TL, Schaffer AA, Zhang JH, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402CrossRefPubMedCentralPubMedGoogle Scholar
  2. Angelini P, Rubini A, Gigante D, Reale L, Pagiotti R, Venanzoni R (2012) The endophytic fungal communities associated with the leaves and roots of the common reed (Phragmites australis) in Lake Trasimeno (Perugia, Italy) in declining and healthy stands. Fungal Ecol 5:683–693CrossRefGoogle Scholar
  3. Baker RA, Tatum JH, Nemec S (1990) Antimicrobial activity of naphthoquinones from fusaria. Mycopathologia 111:9–15CrossRefPubMedGoogle Scholar
  4. Bell AA, Wheeler MH, Liu JG, Stipanovic RD (2003) United States Department of Agriculture—Agricultural Research Service studies on polyketide toxins of Fusarium oxysporum f. sp. vasinfectum: potential targets for disease control. Pest Manag Sci 59:736–747CrossRefPubMedGoogle Scholar
  5. Brimble MA, Duncalf LJ, Nairn MR (1999) Pyranonaphthoquinone antibiotics—isolation, structure and biological activity. Nat Prod Rep 16:267–281CrossRefPubMedGoogle Scholar
  6. Hussain H, Krohn K, Ahmed I, Draeger S, Schulz B, Di Pietro S, Pescitelli G (2012) Phomopsinones A-D: four new pyrenocines from endophytic fungus Phomopsis sp. Eur J Org Chem:1783–1789Google Scholar
  7. Jadulco R, Brauers G, Edrada RA, Ebel R, Wray V, Sudarsono PP (2002) New metabolites from sponge-derived fungi Curvularia lunata and Cladosporium herbarum. J Nat Prod 65:730–733CrossRefPubMedGoogle Scholar
  8. Kolařík M, Jankowiak R (2013) Vector affinity and diversity of Geosmithia fungi living on subcortical insects inhabiting Pinaceae species in central and northeastern Europe. Microb Ecol 66:682–700CrossRefPubMedGoogle Scholar
  9. Koyama J, Morita I, Kobayashi N, Osakai T, Usuki Y, Taniguchi M (2005) Structure-activity relations of azafluorenone and azaanthraquinone as antimicrobial compounds. Bioorg Med Chem Lett 15:1079–1082CrossRefPubMedGoogle Scholar
  10. Narasimh N, Gopalkri KS (1974) Naphthoquinone pigments from Torula herbarum—structure of methylherbarin. J Antibiot 27:283–287CrossRefGoogle Scholar
  11. Opatz T, Kolshorn H, Thines E, Anke H (2008) Ascomycones A-C, heptaketide metabolites from an unidentified ascomycete. J Nat Prod 71:1973–1976CrossRefPubMedGoogle Scholar
  12. Panno L, Bruno M, Voyron S, Anastasi A, Gnavi G, Miserere L, Varese GC (2013) Diversity, ecological role and potential biotechnological applications of marine fungi associated to the seagrass Posidonia oceanica. New Biotechnol 30:685–694CrossRefGoogle Scholar
  13. Paranagama PA, Wijeratne EMK, Burns AM, Marron MT, Gunatilaka MK, Arnold AE, Gunatilaka AAL (2007) Heptaketides from Corynespora sp. inhabiting the cavern beard lichen, Usnea cavernosa: first report of metabolites of an endolichenic fungus. J Nat Prod 70:1700–1705CrossRefPubMedGoogle Scholar
  14. Parisot D, Devys M, Ferezou JP, Barbier M (1983) Pigments from Nectria haematococca, anhydrofusarubin and nectriafurone. Phytochemistry 22:1301–1303CrossRefGoogle Scholar
  15. Parisot D, Devys M, Barbier M (1989) 5-Deoxybostrycoidin, a new metabolite produced by the fungus Necteria haematococca (Berk and Br) WR. Z Naturforsch B J Chem Sci 44:1473–1474Google Scholar
  16. Parisot D, Devys M, Barbier M (1992) Heptaketide derived polyenes from the fungus Necteria haematococca. Phytochemistry 31:4357–4358CrossRefGoogle Scholar
  17. Pažoutová S, Šrůtka P, Holuša J, Chudíčková M, Kubátová A, Kolařík M (2012) Liberomyces gen. nov. with two new species of endophytic coelomycetes from broadleaf trees. Mycologia 104:198–210CrossRefPubMedGoogle Scholar
  18. Piggott MJ (2005) Naphtho[2,3-c]furan-4,9-diones and related compounds: theoretically interesting and bioactive natural and synthetic products. Tetrahedron 61:9929–9954CrossRefGoogle Scholar
  19. Qiancutrone JF, Gao Q, Huang S, Klohr SE, Veitch JA, Shu YZ (1994) Arthrinone, a novel fungal metabolite from Arthrinium sp. FA-1744. J Nat Prod 57:1656–1660CrossRefGoogle Scholar
  20. Qin S, Krohn K, Hussain H, Schulz B, Draeger S (2011) Pestalotheols E-H: antimicrobial metabolites from an endophytic fungus isolated from the tree Arbutus unedo. Eur J Org Chem: 5163–5166Google Scholar
  21. Schüffler A, Liermann JC, Kolshorn H, Opatz T, Anke H (2009a) Isolation, structure elucidation, and biological evaluation of the unusual heterodimer chrysoxanthone from the ascomycete IBWF11-95A. Tetrahedron Lett 50:4813–4815CrossRefGoogle Scholar
  22. Schüffler A, Liermann JC, Kolshorn H, Opatz T, Anke H (2009b) New naphthoquinone derivatives from the ascomycete IBWF79B-90A. Z Naturforsch C Biosci 64:25–31Google Scholar
  23. Sheldrick GM (2008) A short history of SHELX. Acta Crystallogr A 64:112–122CrossRefPubMedGoogle Scholar
  24. Shushni MAM, Mentel R, Lindequist U, Jansen R (2009) Balticols A-F, new naphthalenone derivatives with antiviral activity, from an ascomycetous fungus. Chem Biodivers 6:127–137CrossRefPubMedGoogle Scholar
  25. Shushni MAM, Singh R, Mentel R, Lindequist U (2011) Balticolid: a new 12-membered macrolide with antiviral activity from an ascomycetous fungus of marine origin. Mar Drugs 9:844–851CrossRefPubMedCentralPubMedGoogle Scholar
  26. Shushni MAM, Azam F, Lindequist U (2013) Oxasetin from Lophiostoma sp of the Baltic sea: identification, in silico binding mode prediction and antibacterial evaluation against fish pathogenic bacteria. Nat Prod Comm 8:1223–1226Google Scholar
  27. Simamura E, Hirai KI, Shimada H, Koyama J, Niwa Y, Shimizu S (2006) Furanonaphthoquinones cause apoptosis of cancer cells by inducing the production of reactive oxygen species by the mitochondrial voltage-dependent anion channel. Cancer Biol Ther 5:1523–1529CrossRefPubMedGoogle Scholar
  28. Sperry J, Bachu P, Brimble MA (2008) Pyranonaphthoquinones—isolation, biological activity and synthesis. Nat Prod Rep 25:376–400CrossRefPubMedGoogle Scholar
  29. Sperry J, Yuen TY, Brimble MA (2009) Enantioselective synthesis of the 3C-protease inhibitor (−)-thysanone by a Stauton-Weinreb annulation strategy. Synthesis 2009:2561–2569CrossRefGoogle Scholar
  30. Stipanovic RD, Zhang JX, Bruton BD, Wheeler MH (2004) Isolation and identification of hexaketides from a pigmented Monosporascus cannonballus isolate. J Agric Food Chem 52:4109–4112CrossRefPubMedGoogle Scholar
  31. Suetrong S, Schoch CL, Spatafora JW, Kohlmeyer J, Volkmann-Kohlmeyer B, Sakayaroj J, Phongpaichit S, Tanaka K, Hirayama K, Jones EBG (2009) Molecular systematics of the marine Dothideomycetes. Stud Mycol 64:155–173CrossRefPubMedCentralPubMedGoogle Scholar
  32. Tatum JH, Baker RA, Berry RE (1987) Naphthofurans produced by Fusarium oxysporum isolated from citrus. Phytochemistry 26:2499–2500CrossRefGoogle Scholar
  33. Thomson RH (1971) Naturally occurring quinones, 2nd edn. Academic Press, New YorkGoogle Scholar
  34. Van Wagoner RM, Mantle PG, Wright JLC (2008) Biosynthesis of scorpinone, a 2-azaanthraquinone from Amorosia littoralis, a fungus from marine sediment. J Nat Prod 71:426–430CrossRefPubMedGoogle Scholar
  35. Whyte AC, Gloer KB, Gloer JB, Koster B, Malloch D (1997) New antifungal metabolites from the coprophilous fungus Cercophora sordarioides. Can J Chem 75:768–772CrossRefGoogle Scholar
  36. Yamamoto Y, Kinoshita Y, Thor GR, Hasumi M, Kinoshita K, Koyama K, Takahashi K, Yoshimura I (2002) Isofuranonaphthoquinone derivatives from cultures of the lichen Arthonia cinnabarina (DC.) Wallr. Phytochemistry 60:741–745CrossRefPubMedGoogle Scholar

Copyright information

© Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i. 2014

Authors and Affiliations

  • Eva Stodůlková
    • 1
  • Petr Man
    • 1
  • Marek Kuzma
    • 1
  • Jan Černý
    • 2
  • Ivana Císařová
    • 3
  • Alena Kubátová
    • 4
  • Milada Chudíčková
    • 1
  • Miroslav Kolařík
    • 1
    • 4
  • Miroslav Flieger
    • 1
  1. 1.Institute of Microbiology of the ASCR, v.v.i.Prague 4Czech Republic
  2. 2.Department of Cell Biology, Faculty of ScienceCharles UniversityPragueCzech Republic
  3. 3.Department of Inorganic Chemistry, Faculty of ScienceCharles UniversityPrague 2Czech Republic
  4. 4.Department of Botany, Faculty of ScienceCharles UniversityPrague 2Czech Republic

Personalised recommendations