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Epicoccum Species as Potent Factories for the Production of Compounds of Industrial, Medical, and Biological Control Applications Volume 14 - Issue 3

Waill A Elkhateeb and Ghoson M Daba*

  • Department of Chemistry of Microbial Natural Products, National Research Center, Egypt

Received: January 31, 2019;   Published: February 11, 2019

*Corresponding author: Ghoson Mosbah Daba, Department of Chemistry of Microbial Natural Products, National Research Center, Egypt

DOI: 10.26717/BJSTR.2019.14.002541

Abstract PDF


Epicoccum is an endophytic fungus famous for its application in the biocontrol of numerous phytopathogenic fungi. Moreover, Epicoccum Sp. are known for their capability of producing various biologically active compounds with medical applications as antioxidant, antimicrobial, and anticancer agents. In addition to pigments formation and their industrial application. The aim of this review is to highlight the diversity of compounds produced by Epicoccum sp. and pointing out their medical, bio-control, and industrial applications.

Keywords: Epicoccum; Biological Control; Biotechnology; Secondary Metabolites


Discovering new applications for currently known bioactive metabolites and/ or exploring novel biologically active metabolites are of critical need nowadays due to the current increasing dilemma of microbial resistance to available and used antibiotics and therapeutic agents, beside the emergence of new life threatening diseases. These problems have encouraged scientists to look for unconventional sources in order to find novel compounds. Fungi are promising sources for a wide variety of vital metabolites such as alkaloids, flavonoids, phenols, steroids and terpenoids [1-3]. Fungi capacity to synthesize variety of new bioactive metabolites forced researchers to explore these avenues. Epicoccum is an ascomycotic, endophytic fungus that is commonly isolated from different sources in moderate frequencies [4-6]. E. nigrum is famous for its successful applications in the bio-control of many phyto-pathogens [7-13], also for its ability to produce diverse classes of chemically, structurally, and biologically diverse secondary metabolites [13-17]. The aim of this review is to provide information about secondary metabolites of Epicoccum and their promising and current applications. Highlighting the importance of rich sources of biologically active compounds can contribute in encouraging searching for novel sources of potent compounds to face current needs for antimicrobial agents to overcome microbial antibiotic resistance, and to discover drugs for existing life-threating diseases.

Secondary Metabolites of Epicoccum Species

Epicoccum Sp. produces variety of secondary metabolites such as polyketides, polyketide hybrids, diketopiperazines, Siderophores, Carotenoid, and others (Table 1). Majority of these compounds exert promising biological activities such as antioxidant, antimicrobial, anticancer, in addition to potential industrial applications of pigments produced from E. nigrum as a likely safe, nontoxic, and non-pathogenic fungus. Among the important biologically active compounds produced by Epicoccum spp., the anticancer drug, taxol [18]. Also, epicocconone which is known commercially as fluorophore and is used in cell staining and in gel electrophoresis for protein detection [19,20], D8646-2-6 which is a telomerase inhibitor [21,22], in addition to many potential factories for silver nano-particles production such as Orsellinic acid and Curvularin.

Table 1: some secondary metabolites produced by Epicoccum species and their biotechnological applications.


Epicoccum Spp. As Biocontrol Agents

Epicoccum spp. have proven to be a potent biocontrol agents against many phytopathgenic fungi, specially Botrytis cinerea waxflower [23], Claviceps africana in sorghum [24], Pythium spp. infecting cotton [9], Rhizoctonia solani infecting potato plants [25], and Sclerotinia sclerotiorum in sunflower [26], Phytophthora infestans [27], phytoplasma in apple trees [28] and Monilinia spp. in peaches and nectarines [29-33] and against other plant pathogenic fungi [10,11,34,35].The action mechanisms exhibited by E. nigrum as a biocontrol agent varies from reducing host stem disease severity index, and growing along the fungal pathogen hyphae and inducing its lysis [36], or through causing degradation of the pathogen protoplast, malformation in its hyphae, and leakage of cytoplasm [37]. The polyketide, Flavipin, produced by many Epicoccum Sp is the reason causing growth inhibition of numerous phytopathogenic fungi [25,28,38-41]. On the other hand, Epicolactone isolated from E. nigrum has antifungal activity and can induce root growth [42- 57]. All those studies support using Epicoccum species in different host plants as a safe biological control agent and encourage deep investigations for further understanding of the physiological and molecular aspects of this interaction [57-62].


Emerging of microbial resistance, spread of life-threatening diseases, and biological control of pathogens destroying economically important crops, are serious problems that encourage scientists to search for unconventional sources for novel compounds with biological activities. Fungi are promising sources for such compounds due to their ability to produce assortment of secondary metabolites that could be, if truly investigated, the solution for currently serious problems. Epicoccum is one of the pioneer fungi in this field with proven potent ability as promising biotechnological tool to produce industrially, and biologically diverse metabolites.


  1. Calvo AM, Wilson RA, Bok J W, Keller NP (2002) Relationship between secondary metabolism and fungal development. Microbiology and molecular biology reviews 66(3): 447-459.
  2. Joel EL, Bhimba BV (2013) Evaluation of secondary metabolites from mangrove associated fungi Meyerozyma guilliermondii. Alexandria J Med 49(3): 189-194.
  3. Nisa H, Kamili AN, Nawchoo IA, Shafi S, Shameem N, et al. (2015) Fungal endophytes as prolific source of phytochemicals and other bioactive natural products: a review. Microb Pathog 82: 50-59.
  4. Waill A Elkhateeb (2005) Some mycological, phytopathological and physiological studies on mycobiota of selected newly reclaimed soils in Assiut governorate, Egypt [master thesis]. Assiut, Egypt: Faculty of Science, Assiut University (Doctoral dissertation).
  5. Mims CW, Richardson EA (2005) Ultrastructure of sporodochium and conidium development in the anamorphic fungus Epicoccum nigrum. Botany 83(10): 1354-1363.‏
  6. Arnold AE (2007) Understanding the diversity of foliar endophytic fungi: progress, challenges, and frontiers. Fungal biology reviews 21(2- 3): 51-66.
  7. Kortekamp A (1997) Epicoccum nigrum LINK: A biological control agent of Plasmopara viticola (BERK. et CURT.). Vitis, 36(4): 215-216.
  8. Pieckenstain FL, Bazzalo ME, Roberts AM, Ugalde RA (2001) Epicoccum purpurascens for biocontrol of Sclerotinia head rot of sunflower. Mycological Research 105(1): 77-84.‏
  9. Hashem M, Ali E (2004) Epicoccum nigrum as biocontrol agent of Pythium damping-off and root-rot of cotton seedlings. Archives of Phytopathology and Plant Protection 37(4): 283-297.
  10. Larena I, Torres R, De Cal A, Liñán M, Melgarejo P, et al. (2005) Biological control of postharvest brown rot (Monilinia spp.) of peaches by field applications of Epicoccum nigrum. Biological Control 32(2): 305-310.
  11. Mari M, Torres R, Casalini L, Lamarca N, Mandrin JF, et al. (2007) Control of post-harvest brown rot on nectarine by Epicoccum nigrum and physico-chemical treatments. Journal of the Science of Food and Agriculture 87(7): 1271-1277.
  12. De Cal A, Larena I, Linan M, Torres R, Lamarca N, et al. (2009) Population dynamics of Epicoccum nigrum, a biocontrol agent against brown rot in stone fruit. Journal of applied microbiology 106(2): 592-605.
  13. Braga RM, Padilla G, Araújo WL (2018) The biotechnological potential of Epicoccum sp.: diversity of secondary metabolites. Critical reviews in microbiology 44(6): 759-778.
  14. Shu YZ, Ye Q, Li H, Kadow KF, Hussain RA, et al. (1997) Orevactaene, 1 a novel binding inhibitor of HIV-1 rev protein to Rev response element (RRE) from Epicoccum nigrum WC47880. Bioorganic & Medicinal Chemistry Letters, 7(17): 2295-2298.‏
  15. Fávaro LC, Sebastianes FL, Araújo WL (2012) Epicoccum nigrum P16, a sugarcane endophyte, produces antifungal compounds and induces root growth. PLoS One 7: e36826.
  16. Fatima N, Ismail T, Muhammad SA, Jadoon M, Ahmed S, et al. (2016) Epicoccum sp., an emerging source of unique bioactive metabolites. Acta poloniae pharmaceutica 73(1): 13-21.
  17. Perveen I, Raza MA, Iqbal T, Naz I, Sehar S, et al. (2017) Isolation of anticancer and antimicrobial metabolites from Epicoccum nigrum; endophyte of Ferula sumbul. Microbial pathogenesis 110: 214-224.
  18. Somjaipeng S, Medina A, Kwasna H, Ordaz Ortiz J, Magan N (2015) Isolation, identification, and ecology of growth and taxol production by an endophytic strain of Paraconiothyrium variabile from English yew trees (Taxus baccata). Fungal Biol 119(11): 1022-1031.
  19. Bell PJL, Karuso P (2003) Epicocconone, a novel fluorescent compound from the fungus Epicoccum nigrum. J Am Chem Soc 125(31): 9304-9305.
  20. Choi HY, Veal DA, Karuso P (2006) Epicocconone, a new cellpermeable long Stokes’ shift fluorescent stain for live cell imaging and multiplexing. J Fluoresc 16(4): 475-482.
  21. Kanai A, Takeda Y, Kuramochi K, Nakazaki A, Kobayashi S (2007) Synthetic study on telomerase inhibitor, D8646-2-6: synthesis of the key intermediate using Sn(OTf)2 or Sc(OTf)3 mediated aldol-type reaction and Stille coupling. Chem Pharm Bull 55(3): 495-499.
  22. Peng J, Jiao J, Li J, Wang W, Gu Q, et al. (2012) Pyronepolyene C-glucosides with NF-jB inhibitory and anti-influenza A viral (H1N1) activities from the sponge-associated fungus Epicoccum sp. JJY40. Bioorg Med Chem Lett 22(9): 3188-3190.
  23. Mohamed AM (2015) One-step functionalization of silver nanoparticles using the orsellinic acid compound isolated from the endophytic fungus Epicoccum nigrum: Characterization and antifungal activity. Int J Nano Chem 1(3): 103-110.
  24. Abdel Hafez SII, Nafady NA, Abdel Rahim IR, Shaltout AM, Daros JA, et al. (2017) Biosynthesis of silver nano- particles using the compound curvularin isolated from the endophytic fungus Epicoccum nigrum: characterization and antifungal activity. J Pharm Appl Chem 3(2): 135- 146.
  25. Bamford PC, Norris GL, Ward G (1961) Flavipin production by Epicoccum spp. Transactions of the British Mycological Society 44(3): 354-356.‏
  26. Burge WR, Buckley LJ, Sullivan JD, McGrattan CJ, Ikawa M (1976) Isolation and biological activity of the pigments of the mold Epicoccum nigrum. J Agric Food Chem 24(3): 555-559.
  27. Brown AE, Finlay R, Ward JS (1987) Antifungal compounds produced by Epicoccum purpurascens against soil-borne plant pathogenic fungi. Soil Biol Biochem 19(6): 657-664.
  28. Madrigal C, Tadeo JL, Melgarejo P (1991) Relationship between flavipin production by Epicoccum nigrum and antagonism against Monilinia laxa. Mycol Res 95(12): 1375-1381.
  29. Ishikawa Y, Ito T, Lee K (1996) Inhibition of sardine flesh lipoxygenase by a new antioxidant from Aspergillus terreus. J Jpn Oil Chem Soc 45(12): 1321-1325.
  30. Lee NH, Gloer JB, Wicklow DT (2007) Isolation of chromanone and isobenzofuran derivatives from a fungicolous isolate of Epicoccum purpurascens. Bull Korean Chem Soc 28: 877-879.
  31. Kemami Wangun HV, Ishida K, Hertweck C (2008) Epicoccalone, a coumarin-type chymotrypsin inhibitor, and isobenzofuran congeners from an Epicoccum sp. associated with a tree fungus. European J Org Chem 22: 3781-3784.
  32. El Amrani M, Lai D, Debbab A, Aly AH, Siems K, et al. (2014) Protein kinase and HDAC inhibitors from the endophytic fungus Epicoccum nigrum. J Nat Prod 77(1): 49-56.
  33. Abdel Lateff A, Fisch KM, Wright AD, Konig GM (2003) A new antioxidant isobenzofuranone derivative from the algicolous marine fungus Epicoccum sp. Planta Med 69(9): 831-834.
  34. Cabras A, Mannoni MA, Serra S, Andolfi A, Fiore M, et al. (2006) Occurrence, isolation and biological activity of phytotoxic metabolites produced in vitro by Sphaeropsis sapinea, pathogenic fungus of Pinus radiata. Eur J Plant Pathol 115: 187-193.
  35. da Silva Araújo FD, de Lima Fávaro LC, Araújo WL, de Oliveira FL, Aparicio R, et al. (2012) Epicolactone–natural product isolated from the sugarcane endophytic fungus Epicoccum nigrum. European Journal of Organic Chemistry 27: 5225-5230.
  36. Herzner G, Schlecht A, Dollhofer V, Parzefall C, Harrar K, et al. (2013) Larvae of the parasitoid wasp Ampulex compressa sanitize their host, the American cockroach, with a blend of antimicrobials. Proc Natl Acad Sci USA 110(4): 1369-1374.
  37. Ramos HP, Simao MR, de Souza JM, Magalhaes LG, Rodrigues V, et al. (2013) Evaluation of dihydroisocou-marins produced by the endophytic fungus Arthrinium state of Apiospora montagnei against Schistosoma mansoni. Nat Prod Res 27(23): 2240-2243.
  38. Wang J, Wang G, Zhang Y, Zheng B, Zhang C, et al. (2014) Isolation and identification of an endophytic fungus Pezicula sp. in Forsythia viridissima and its secondary metabolites. World J Microbiol Biotechnol 30(10): 2639-2644.
  39. Talontsi FM, Dittrich B, Schuffler A, Sun H, Laatsch H (2013) Epicoccolides: antimicrobial and antifungal polyketides from an endophytic fungus Epicoccum sp. associated with Theobroma cacao. Eur J Org Chem 2013(15): 3174-3180.
  40. Dzoyem JP, Melong R, Tsamo AT, Maffo T, Kapche DGWF, et al. (2017) Cytotoxicity, antioxidant and antibacterial activity of four compounds produced by an endophytic fungus Epicoccum nigrum associated with Entada abyssinica. Brazilian J Pharmacogn 27(2): 251-253.
  41. Kemami Wangun HV, Hertweck C (2007) Epicoccarines A, B and epipyridone: tetramic acids and pyridone alkaloids from an Epicoccum sp. associated with the tree fungus Pholiota squarrosa. Org Biomol Chem 5(11): 1702-1705.
  42. Li C, Sarotti AM, Yang B, Turkson J, Cao S (2017) A new Nmethoxypyridone from the co-cultivation of Hawaiian endophytic fungi Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062. Molecules 22(7): E1166.
  43. Wright AD, Osterhage C, König GM (2003) Epicoccamide, a novel secondary metabolite from a jellyfish-derived culture of Epicoccum purpurascens. Organic & biomolecular chemistry 1(3): 507-510.
  44. Wangun H, Dahse H, Hertweck C (2007) Epicoccamides B-D, glycosylated tetramic acid derivatives from an Epicoccum sp. associated with the tree fungus Pholiota squarrosa. J Nat Prod 70(11): 1800-1803.
  45. Zhang Y, Liu S, Che Y, Liu X (2007) Epicoccins A-D, epipolythiodioxopiperazines from a Cordyceps-colonizing isolate of Epicoccum nigrum. J Nat Prod 70(9): 1522-1525.
  46. Guo H, Sun B, Gao H, Chen X, Liu S, et al. (2009) Journal of natural products 72(12): 2115-2119.
  47. Wang JM, Ding GZ, Fang L, Dai JG, Yu SS, et al. (2010) Journal of natural products 73(7): 1240-1249.
  48. Baute MA, Deffieux G, Baute R, Neveu A (1978) New antibiotics from the fungus Epicoccum nigrum. The journal of Antibiotics 31(11): 1099-1101. ‏
  49. Xia X, Zhang J, Zhang Y, Wei F, Liu X, et al. (2012) Pimarane diterpenes from the fungus Epicoccum sp. HS-1 associated with Apostichopus japonicus. Bioorg Med Chem Lett 22(8): 3017-3019.
  50. Foppen FH, Gribanovski Sassu O (1968) Lipids produced by Epicoccum nigrum in submerged culture. Biochem J 106(1): 97-100.
  51. Frederick CB, Bentley MD, Shive W (1981) Structure of triornicin, a new siderophore. Biochemistry 20(9): 2436-2438.
  52. Beasley DR, Joyce DC, Coates LM, Wearing AH (2001) Saprophytic microorganisms with potential for biological control of Botrytis cinerea on Geraldton waxflower flowers. Aust J Exp Agric 41(5): 697-703.
  53. Bhuiyan SA, Ryley MJ, Galea VJ, Tay D (2003) Evaluation of potential biocontrol agents against Claviceps africana in vitro and in vivo. Plant Pathol 52(1): 60-67.
  54. Lahlali R, Hijri M (2010) Screening, identification and evaluation of potential biocontrol fungal endophytes against Rhizoctonia solani AG3 on potato plants. FEMS Microbiol Lett 311(2): 152-159.
  55. Li Y, Xia LQ, Wang YNN, Liu XY, Zhang CH, et al. (2013) The inhibitory effect of Epicoccum nigrum strain XF1 against Phytophthora infestans. Biol Control 67(3): 462-468.
  56. Musetti R, Grisan S, Polizzotto R, Martini M, Paduano C, et al. (2011) Interactions between ‘Candidatus Phytoplasma mali’ and the apple endophyte Epicoccum nigrum in Catharanthus roseus plants. Journal of Applied Microbiology 110(3): 746-756.
  57. Larena I, Melgarejo P (2009) Development of a new strategy for monitoring Epicoccum nigrum 282, a biological control agent used against brown rot caused by Monilinia spp. in peaches. Postharvest Biology and Technology 54(2): 63-71.
  58. Peng G, Sutton JC (1991) Evaluation of microorganisms for biocontrol of Botrytis cinerea in strawberry. Can J Plant Pathol 13(3): 247-257.
  59. Madrigal C, Pascual S, Melgarejo P (1994) Biological control of peach twig blight (Monilinia laxa) with Epicoccum nigrum. Plant Pathol 43(3): 554-561.
  60. Xiao Y, Li HX, Li C, Wang JX, Li J, et al. (2013) Antifungal screening of endophytic fungi from Ginkgo biloba for discovery of potent antiphytopathogenic fungicides. FEMS Microbiol Lett 339(2): 130-136.
  61. Ye Y, Xiao Y, Ma L, Li H, Xie Z, et al. (2013) Flavipin in Chaetomium globosum CDW7, an endophytic fungus from Ginkgo biloba, contributes to antioxidant activity. Appl Microbiol Biotechnol 97(16): 7131-7139.
  62. . de Lima Favaro LC, de Souza Sebastianes FL, Araújo WL (2012) Epicoccum nigrum P16, a sugarcane endophyte, produces antifungal compounds and induces root growth. PLoS One 7(6): e36826.