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New synergistic co-culture of Corylus avellana cells and Epicoccum nigrum for paclitaxel production

  • Fermentation, Cell Culture and Bioengineering - Original Paper
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Paclitaxel is a main impressive chemotherapeutic agent with unique mode of action and broad-spectrum activity against cancers. Hazel (Corylus avellana) is a paclitaxel-producing species through bioprospection. Endophytic fungi have significant roles in plant paclitaxel production. This study evaluated the effect of co-culture of C. avellana cells and paclitaxel-producing endophytic fungus, Epicoccum nigrum strain YEF2 and also the effect of elicitors derived from this fungal strain on paclitaxel production. The results clearly revealed that co-culture of C. avellana cells and E. nigrum was more effective than elicitation of C. avellana cells by only cell extract or culture filtrate of this fungal strain. Co-culture of C. avellana cells and E. nigrum surpassed monocultures in terms of paclitaxel production designating their synergistic interaction potential. Fungal inoculum amount, co-culture establishment time and co-culture period were important factors for achieving the maximum production of paclitaxel in this co-culture system. The highest total yield of paclitaxel (404.5 µg L−1) was produced in co-culture established on 13th day using 3.2% (v/v) of E. nigrum mycelium suspension, which was about 5.5 and 136.6 times that in control cultures of C. avellana cells and E. nigrum, respectively. This is the first report on positive effect of co-culture of paclitaxel-producing endophytic fungus and non-host plant cells for enhancing paclitaxel production.

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References

  1. Awad V, Kuvalekar A, Harsulkar A (2014) Microbial elicitation in root cultures of Taverniera cuneifolia (Roth) Arn. for elevated glycyrrhizic acid production. Ind Crops Prod 54:13–16. https://doi.org/10.1016/j.indcrop.2013.12.036

    Article  CAS  Google Scholar 

  2. Baldi A, Srivastava AK, Bisaria VS (2009) Fungal elicitors for enhanced production of secondary metabolites in plant cell suspension cultures. In: Varma A, Kharkwal AC (eds) Symbiotic fungi, soil biology, vol 18. Springer, Berlin, pp 373–380. https://doi.org/10.1007/978-3-540-95894-9_23

    Chapter  Google Scholar 

  3. Bestoso F, Ottaggio L, Armirotti A, Balbi A, Damonte G, Degan P, Mazzei M, Cavalli F, Ledda B, Miele M (2006) In vitro cell cultures obtained from different explants of Corylus avellana produce Taxol and taxanes. BMC Biotechnol 6:45–56. https://doi.org/10.1186/1472-6750-6-45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dai CC, Yu BY, Xu ZL, Yuan S (2003) Effect of environmental factors on growth and fatty acid composition of five endophytic fungi from Sapium sebiferum. J Appl Ecol 14:1525–1528

    CAS  Google Scholar 

  5. Ding CH, Wang QB, Guo S, Wang ZY (2018) The improvement of bioactive secondary metabolites accumulation in Rumex gmelini Turcz through co-culture with endophytic fungi. Braz J Microbiol 49(2):362–369. https://doi.org/10.1016/j.bjm.2017.04.013

    Article  CAS  PubMed  Google Scholar 

  6. Esmaeilzadeh Bahabadi S, Sharifi M, Behmanesh M, Safaie N, Murata J, Araki R, Yamagaki T, Satake H (2014) Time-course changes in fungal elicitor-induced lignan synthesis and expression of the relevant genes in cell cultures of Linum album. J Plant Physiol 169(2012):487–491. https://doi.org/10.1016/j.jplph.2011.12.006

    Article  CAS  Google Scholar 

  7. Espinosa-Leal CA, Puente-Garza CA, García-Lara S (2018) In vitro plant tissue culture: means for production of biological active compounds. Planta 247:1–18. https://doi.org/10.1007/s00425-018-2910-1

    Article  CAS  Google Scholar 

  8. Faeth SH, Fagan WF (2002) Fungal endophytes: common host plant symbionts but uncommon mutualists. Integr Comp Biol 42:360–368. https://doi.org/10.1093/icb/42.2.360

    Article  Google Scholar 

  9. Flores-Bustamante ZR, Rivera-Orduna FN, Martinez-Cardenas A, Flores-Cotera LB (2010) Microbial paclitaxel: advances and perspectives. J Antibiot 63:460–467. https://doi.org/10.1038/ja.2010.83

    Article  CAS  PubMed  Google Scholar 

  10. Gibson DM, Ketchum REB, Vance NC, Christen AA (1993) Initiation and growth of cell lines of Taxus brevifolia (Pacific yew). Plant Cell Rep 12:479–482. https://doi.org/10.1007/BF00236091

    Article  CAS  PubMed  Google Scholar 

  11. GraphPad Prism 5. GraphPad Software Inc (2005) San Diego CA

  12. Hoffman A, Khan W, Worapong J, Strobel G, Griffin D, Arbogast B, Barofsky D, Boone RB, Ning L, Zheng P, Daley L (1998) Bioprospecting for Taxol in angiosperm plant extracts-using high performance liquid chromatography thermospray mass spectrometry to detect the anticancer agent and its related metabolites in Filbert trees. Spectroscopy 13(6):22–32

    CAS  Google Scholar 

  13. Jia M, Chen L, Xin HL, Zheng CJ, Rahman K, Han T, Qin LP (2016) A friendly relationship between endophytic fungi and medicinal plants: a systematic review. Front Microbiol 9(7):906. https://doi.org/10.3389/fmicb.2016.00906

    Article  Google Scholar 

  14. Kusari S, Hertweck C, Spiteller M (2012) Chemical ecology of endophytic fungi: origins of secondary metabolites. Chem Biol 19(7):792–798. https://doi.org/10.1016/j.chembiol.2012.06.004

    Article  CAS  PubMed  Google Scholar 

  15. Li YC, Tao WY (2009) Interactions of taxol-producing endophytic fungus with its host (Taxus spp.) during taxol accumulation. Cell Biol Int 33(1):106–112. https://doi.org/10.1016/j.cellbi.2008.10.007

    Article  CAS  PubMed  Google Scholar 

  16. Li YC, Tao WY, Cheng L (2009) Paclitaxel production using co-culture of Taxus suspension cells and paclitaxel-producing endophytic fungi in a co-bioreactor. Appl Microbiol Biotechnol 83(2):233. https://doi.org/10.1007/s00253-009-1856-4

    Article  CAS  PubMed  Google Scholar 

  17. Miele M, Mumot AM, Zappa A, Romano P, Ottaggio L (2012) Hazel and other sources of paclitaxel and related compounds. Phytochem Rev 11:211–225. https://doi.org/10.1007/s11101-012-9234-8

    Article  CAS  Google Scholar 

  18. Ming Q, Su C, Zheng C, Jia M, Zhang Q, Zhang H, Qin L (2013) Elicitors from the endophytic fungus Trichoderma atroviride promote Salvia miltiorrhiza hairy root growth and tanshinone biosynthesis. J Exp Bot 64(18):5687–5694. https://doi.org/10.1093/jxb/ert342

    Article  CAS  PubMed  Google Scholar 

  19. Murashige T, Skoog F (1962) A revised medium for rapid growth and bioassays with tobacco tissue cultures. Physiol Plant 15:473–497. https://doi.org/10.1111/j.1399-3054.1962.tb08052.x

    Article  CAS  Google Scholar 

  20. Nadeem M, Rikhari HC, Kumar A, Palni LMS, Nandi SK (2002) Taxol content in the bark of Himalayan Yew in relation to tree age and sex. Phytochemistry 60(6):627–631. https://doi.org/10.1016/S0031-9422(02)00115-2

    Article  CAS  PubMed  Google Scholar 

  21. Plassard CS, Mousain DG, Salsac LE (1982) Estimation of mycelial growth of basidiomycetes by means of chitin determination. Phytochemistry 21(2):345–348. https://doi.org/10.1016/S0031-9422(00)95263-4

    Article  CAS  Google Scholar 

  22. Roberts SC (2007) Production and engineering of terpenoids in plant cell culture. Nat Chem Biol 3(7):387. https://doi.org/10.1038/nchembio.2007.8

    Article  CAS  PubMed  Google Scholar 

  23. Salehi M, Moieni A, Safaie N (2017) A novel medium for enhancing callus growth of hazel (Corylus avellana L.). Sci Rep 7(1):15598. https://doi.org/10.1038/s41598-017-15703-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Salehi M, Moieni A, Safaie N (2018) Elicitors derived from hazel (Corylus avellana L.) cell suspension culture enhance growth and paclitaxel production of Epicoccum nigrum. Sci Rep 8(1):12053. https://doi.org/10.1038/s41598-018-29762-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Salehi M, Moieni A, Safaie N, Farhadi S (2019) Elicitors derived from endophytic fungi Chaetomium globosum and Paraconiothyrium brasiliense enhance paclitaxel production in Corylus avellana cell suspension culture. Plant Cell Tissue Organ Cult 136(1):161–171. https://doi.org/10.1007/s11240-018-1503-9

    Article  CAS  Google Scholar 

  26. SAS 9.3. SAS Institute Inc. (2011) Cary, NC, USA

  27. Schiff PB, Fant J, Horwitz SB (1979) Promotion of microtubule assembly in vitro by taxol. Nature 277(5698):665–667. https://doi.org/10.1038/277665a0

    Article  CAS  PubMed  Google Scholar 

  28. Service RF (2000) Hazel trees offer new source of cancer drug. Science 288:27–28. https://doi.org/10.1126/science.288.5463.27a

    Article  PubMed  Google Scholar 

  29. Sherameti I, Shahollari B, Venus Y, Altschmied L, Varma A, Oelmüller R (2005) The endophytic fungus Piriformospora indica stimulates the expression of nitrate reductase and the starch-degrading enzyme glucan water dikinase in tobacco and Arabidopsis roots through a homeodomain transcription factor that binds to a conserved motif in their promoters. J Biol Chem 280:26241–26247. https://doi.org/10.1074/jbc.M500447200

    Article  CAS  PubMed  Google Scholar 

  30. Soliman S, Trobacher C, Tsao R, Greenwood J, Raizada M (2013) A fungal endophyte induces transcription of genes encoding a redundant fungicide pathway in its host plant. BMC Plant Biol 13(1):93. https://doi.org/10.1186/1471-2229-13-93

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Soliman SSM, Raizada MN (2013) Interactions between co-habitating fungi elicit synthesis of taxol from an endophytic fungus in host Taxus plants. Front Microbiol 4:1–14. https://doi.org/10.3389/fmicb.2013.00003

    Article  CAS  Google Scholar 

  32. Somjaipeng S, Medina A, Magan N (2016) Environmental stress and elicitors enhance taxol production by endophytic strains of Paraconiothyrium variabile and Epicoccum nigrum. Enzyme Microb Technol 90:69–75. https://doi.org/10.1016/j.enzmictec.2016.05.002

    Article  CAS  PubMed  Google Scholar 

  33. SPSS 15.0 Command Syntax Reference. SPSS Inc. (2006) Chicago Illinois

  34. Stierle A, Strobel G, Stierle D (1993) Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science 260(5105):214–216. https://doi.org/10.1126/science.8097061

    Article  CAS  PubMed  Google Scholar 

  35. Strobel G (2018) The emergence of endophytic microbes and their biological promise. J Fungi (Basel) 4(2):57. https://doi.org/10.3390/jof4020057

    Article  CAS  Google Scholar 

  36. Strobel G, Daisy B (2003) Bioprospecting for microbial endophytes and their natural products. Microbiol Mol Biol Rev 67(4):491–502. https://doi.org/10.1128/MMBR.67.4.491-502.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Venugopalan A, Srivastava S (2015) Enhanced camptothecin production by ethanol addition in the suspension culture of the endophyte, Fusarium solani. Bioresour Technol 188:251–257. https://doi.org/10.1016/j.biortech.2014.12.106

    Article  CAS  PubMed  Google Scholar 

  38. Wang C, Wu J, Mei X (2001) Enhancement of taxol production and excretion in Taxus chinensis cell culture by fungal elicitation and medium renewal. Appl Microb Biotechnol 55(4):404–410. https://doi.org/10.1007/s002530000567

    Article  CAS  Google Scholar 

  39. Wang Y, Dai C, Zhao Y, Peng Y (2011) Fungal endophyte-induced volatile oil accumulation in Atractylodes lancea plantlets is mediated by nitric oxide, salicylic acid and hydrogen peroxide. Process Biochem 46:730–735. https://doi.org/10.1016/j.procbio.2010.11.020

    Article  CAS  Google Scholar 

  40. Wheeler NC, Jech K, Masters S, Brobst SW, Alvarado AB, Hoover AJ, Snade KM (1992) Effects of genetic, epigenetic, and environmental factors on taxol content in Taxus brevifolia and related species. J Nat Prod 55:432–440. https://doi.org/10.1021/np50082a005

    Article  CAS  PubMed  Google Scholar 

  41. Widholm JM (1972) The use of fluorescein diacetate and phenosafranine for determining viability of cultured plant cells. Stain Technol 47:189–194. https://doi.org/10.3109/10520297209116483

    Article  CAS  PubMed  Google Scholar 

  42. Wu ZL, Yuan YJ, Liu JX, Xuan HY, Hu ZD, Sun AC, Hu CX (1999) Study on enhanced production of Taxol from Taxus chinensis var. mairei in biphasic-liquid culture. Acta Bot Sin 41:1108–1113

    CAS  Google Scholar 

  43. Zhai X, Luo D, Li X, Han T, Jia M, Kong Z, Ji J, Rahman K, Qin L, Zheng C (2018) Endophyte Chaetomium globosum D38 promotes bioactive constituents accumulation and root production in Salvia miltiorrhiza. Front Microbiol 8:2694. https://doi.org/10.3389/fmicb.2017.02694

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Authors gratefully acknowledge Research Deputy of Tarbiat Modares University, Tehran, for financial support of this research project.

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Correspondence to Mina Salehi or Ahmad Moieni.

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Salehi, M., Moieni, A., Safaie, N. et al. New synergistic co-culture of Corylus avellana cells and Epicoccum nigrum for paclitaxel production. J Ind Microbiol Biotechnol 46, 613–623 (2019). https://doi.org/10.1007/s10295-019-02148-8

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