Skip to main content
Log in

Alternaria alternata F3, a Novel Taxol-Producing Endophytic Fungus Isolated from the Fruits of Taxus cuspidata: Isolation, Characterization, Taxol Yield Improvement, and Antitumor Activity

  • Original Article
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

In this study, a novel taxol-producing endophytic fungus, strain F3, was isolated from the fruits of Taxus cuspidata and identified as Alternaria alternata according to its macroscopic and microscopic traits and sequence analysis of internal transcribed spacer (ITS). The presence of taxol was detected by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) and confirmed by ultra-high-performance liquid chromatography-electrospray coupled to tandem mass spectrometry (UPLC-ESI–MS/MS) and nuclear magnetic resonance (NMR). The fermentation parameters of strain F3 were then optimized for high taxol production. The maximum taxol yield of 195.4 µg L−1 by A. alternata F3 was observed in 200-mL yeast peptone dextrose (YPD) broth, at an initial pH value of 6.0, supplemented with 0.1 g L−1 sodium acetate, 0.25 g L−1 salicylic acid, and 0.00125 g L−1 silver nitrate and inoculum size 2%, and incubated at 28 °C and 150 rpm for 8 days, which was 2.12-fold compared with the initial yield of taxol. Also, fungal taxol exhibited antitumor activity towards human lung carcinoma (A549) cell line and human cervical carcinoma (Hela) cell line with IC50 values of 3.98 µg mL−1 and 0.35 µg mL−1. Overall, this is the first report on taxol-producing endophytic fungus isolated from the fruits of Taxus. This study offers a novel source for the production of taxol for anticancer treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Wani, M. C., Taylor, H. L., Wall, M. E., Coggon, P., & McPhail, A. T. (1971). Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. Journal of the American Chemical Society, 93(9), 2325–2327. https://doi.org/10.1021/ja00738a045

    Article  CAS  PubMed  Google Scholar 

  2. Wiernik, P. H., Schwartz, E. L., Einzig, A., Strauman, J. J., Lipton, R. B., & Dutcher, J. P. (1987). Phase I trial of taxol given as a 24-hour infusion every 21 days: Responses observed in metastatic melanoma. Journal of Clinical Oncology, 5(8), 1232–1239. https://doi.org/10.1200/jco.1987.5.8.1232

    Article  CAS  PubMed  Google Scholar 

  3. Patel, R. N. (1998). Tour de paclitaxel: Biocatalysis for semisynthesis. Annual Review of Microbiology, 52, 361–395. https://doi.org/10.1146/annurev.micro.52.1.361

    Article  CAS  PubMed  Google Scholar 

  4. Howat, S., Park, B., Oh, I. S., Jin, Y. W., Lee, E. K., & Loake, G. J. (2014). Paclitaxel: Biosynthesis, production and future prospects. New Biotechnology, 31(3), 242–245. https://doi.org/10.1016/j.nbt.2014.02.010

    Article  CAS  PubMed  Google Scholar 

  5. Shankar, N. B. (2019). Developments in taxol production through endophytic fungal biotechnology: A review. Oriental Pharmacy and Experimental Medicine, 19(1), 1–13. https://doi.org/10.1007/s13596-018-0352-8

    Article  CAS  Google Scholar 

  6. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca-A Cancer Journal for Clinicians, 71(3), 209–249. https://doi.org/10.3322/caac.21660

    Article  CAS  PubMed  Google Scholar 

  7. Holton, R. A., Somoza, C., Kim, H. B., Liang, F., Biediger, R. J., Boatman, P. D., Shind-o, M., Smith, C. C., Kim, S. C., Nadizadeh, H., Suzuki, Y., Tao, C. L., Vu, P., Tang, S. H., Zhang, P. S., Murthi, K. K., Gentile, L. N., & Liu, J. H. (1994). First total synthesis of taxol. 1. Functionalization of the B ring. Journal of the American Chemical Society, 116(4), 1597–1598. https://doi.org/10.1021/ja00083a066

    Article  CAS  Google Scholar 

  8. Nicolaou, K. C., Yang, Z., Liu, J. J., Ueno, H., Nantermet, P. G., Guy, R. K., Claiborne, C. F., Renaud, J., Couladouros, E. A., Paulvannan, K., & Sorensen, E. J. (1994). Total synthesis of taxol. Nature, 367(6464), 630–634. https://doi.org/10.1038/367630a0

    Article  CAS  PubMed  Google Scholar 

  9. Li, D., Fu, D. W., Zhang, Y., Ma, X. L., Gao, L. G., Wang, X. H., Zhou, D. P., & Zhao, K. (2017). Isolation, purification, and identification of taxol and related taxanes from taxol-producing fungus Aspergillus niger subsp. taxi. Journal of Microbiology and Biotechnology, 27(8), 1379–1385. https://doi.org/10.4014/jmb.1701.01018

    Article  CAS  PubMed  Google Scholar 

  10. Chandra, S. (2012). Endophytic fungi: Novel sources of anticancer lead molecules. Applied Microbiology and Biotechnology, 95(1), 47–59. https://doi.org/10.1007/s00253-012-4128-7

    Article  CAS  PubMed  Google Scholar 

  11. Wang, X., Wang, C., Sun, Y. T., Sun, C. Z., Zhang, Y., Wang, X. H., & Zhao, K. (2015). Taxol produced from endophytic fungi induces apoptosis in human breast, cervical and ovarian cancer cells. Asian Pacific Journal of Cancer Prevention, 16(1), 125–131. https://doi.org/10.7314/APJCP.2015.16.1.125

    Article  PubMed  Google Scholar 

  12. El-Sayed, E. R., Ahmed, A. S., & Al-Hagar, O. E. A. (2020). Agro-industrial wastes for production of paclitaxel by irradiated Aspergillus fumigatus under solid-state fermentation. Journal of Applied Microbiology, 128(5), 1427–1439. https://doi.org/10.1111/jam.14574

    Article  CAS  PubMed  Google Scholar 

  13. El-Sayed, E. R., Ismaiel, A. A., Ahmed, A. S., Hassan, I. A., & Karam El-Din, A. A. (2019). Bioprocess optimization using response surface methodology for production of the anticancer drug paclitaxel by Aspergillus fumigatus and Alternaria tenuissima: Enhanced production by ultraviolet and gamma irradiation. Biocatalysis and Agricultural Biotechnology, 18, 100996. https://doi.org/10.1016/j.bcab.2019.01.034

    Article  Google Scholar 

  14. El-Sayed, E. R., Ahmed, A. S., Hassan, I. A., Ismaiel, A. A., & El-Din, A. A. (2019). Strain improvement and immobilization technique for enhanced production of the anticancer drug paclitaxel by Aspergillus fumigatus and Alternaria tenuissima. Applied Microbiology and Biotechnology, 103(21–22), 8923–8935. https://doi.org/10.1007/s00253-019-10129-1

    Article  CAS  PubMed  Google Scholar 

  15. Kusari, S., Hertweck, C., & Spitellert, M. (2012). Chemical ecology of endophytic fungi: Origins of secondary metabolites. Chemistry and Biology, 19(7), 792–798. https://doi.org/10.1016/j.chembiol.2012.06.004

    Article  CAS  PubMed  Google Scholar 

  16. 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 

  17. Kuriakose, G. C., Arathi, B., Lakshmanan, M. D., Jiby, M. V., Gudde, R. S., & Jayabhaskaran, C. (2020). Sub-acute toxicity assessment of taxol isolated from Fusarium solani, an endophytic fungus of Taxus brevifolia, in wistar rats and analyzing its cytotoxicity and apoptotic potential in lung cancer cells. Frontiersin Oncology, 10, 538865. https://doi.org/10.3389/fonc.2020.538865

    Article  Google Scholar 

  18. Chakravarthi, B. V. S. K., Das, P., Surendranath, K., Karande, A. A., & Jayabaskaran, C. (2008). Production of paclitaxel by Fusarium solani isolated from Taxus celebica. Journal of Biosciences, 33(2), 259–267. https://doi.org/10.1007/s12038-008-0043-6

    Article  CAS  PubMed  Google Scholar 

  19. Kumaran, R. S., & Hur, B. K. (2009). Screening of species of the endophytic fungus Phomopsis for the production of the anticancer drug taxol. Biotechnology and Applied Biochemistry, 54(1), 21–30. https://doi.org/10.1042/ba20080110

    Article  CAS  PubMed  Google Scholar 

  20. Zhu, J., Li, Y., & Meng, L. (2008). Comparative study on different parts of taxol-producing endophytic fungi from T. chinesis in Taihang Mountain. Biotechnology Bulletin, 4, 191–194.

    Google Scholar 

  21. Li, N., Pan, Z., Zhang, D., Wang, H. X., Yu, B., Zhao, S. P., Guo, J. J., Wang, J. W., Yao, L., & Cao, W. G. (2017). Chemical components, biological activities, and toxicological evaluation of the fruit (aril) of two precious plant species from genus Taxus. Chemistry and Biodiversity, 14(12), e1700305. https://doi.org/10.1002/cbdv.201700305

    Article  CAS  Google Scholar 

  22. Siegle, L., & Pietsch, J. (2018). Taxus ingredients in the red arils of Taxus baccata L. determined by HPLC-MS/MS. Phytochemical Analysis, 29(5), 446–445. https://doi.org/10.1002/pca.2748

    Article  CAS  PubMed  Google Scholar 

  23. Liu, S., Tang, K., Peng, X., & He, P. (2012). Nutritional components of Taxus chinensis var mairei seeds and acute toxicity of its aril. Food Science, 33(19), 298–301.

    CAS  Google Scholar 

  24. Fu, Y. J., Sun, R., Li, S. M., Zhang, R., & Zu, Y. G. (2007). Dynamic space-time variation of the content of paclitaxel in renewable parts of Taxus cuspidata. Chinese Bulletin of Botany, 24(4), 465–469.

    CAS  Google Scholar 

  25. Strobel, G., Yang, X., Sears, J., Kramer, R., Sidhu, R. S., & Hess, W. M. (1996). Taxol from Pestalotiopsis microspora, an endophytic fungus of Taxus wallachiana. Microbiology, 142(Pt2), 435–440. https://doi.org/10.1099/13500872-142-2-435

    Article  CAS  PubMed  Google Scholar 

  26. Li, S., Fu, Y., Zu, Y., Sun, R., Wang, Y., Zhang, L., Luo, H., Gu, C., & Efferth, T. (2009). Determination of paclitaxel and other six taxoids in Taxus species by high-performance liquid chromatography-tandem mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis, 49(1), 81–89. https://doi.org/10.1016/j.jpba.2008.10.006

    Article  CAS  PubMed  Google Scholar 

  27. Ismaiel, A. A., Ahmed, A. S., Hassan, I. A., El-Sayed, E. R., & El-Din, A. A. K. (2017). Production of paclitaxel with anticancer activity by two local fungal endophytes, Aspergillus fumigatus and Alternaria tenuissima. Applied Microbiology and Biotechnology, 101(14), 5831–5846. https://doi.org/10.1007/s00253-017-8354-x

    Article  CAS  PubMed  Google Scholar 

  28. Flores-Bustamante, Z. R., Rivera-Orduna, F. N., Martinez-Cardenas, A., & Flores-Cotera, L. B. (2010). Microbial paclitaxel: Advances and perspectives. Journal of Antibiotics, 63(8), 460–467. https://doi.org/10.1038/ja.2010.83

    Article  CAS  PubMed  Google Scholar 

  29. Mirjalili, M. H., Farzaneh, M., Bonfill, M., Rezadoost, H., & Ghassempour, A. (2012). Isolation and characterization of Stemphylium sedicola SBU-16 as a new endophytic taxol-producing fungus from Taxus baccata grown in Iran. FEMS Microbiology Letters, 328(2), 122–129. https://doi.org/10.1111/j.1574-6968.2011.02488.x

    Article  CAS  PubMed  Google Scholar 

  30. Abdel-Fatah, S. S., El-Batal, A. I., El-Sherbiny, G. M., Khalaf, M. A., & El-Sayed, A. S. (2021). Production, bioprocess optimization and gamma-irradiation of Penicillium polonicum, as a new Taxol producing endophyte from Ginko biloba. Biotechnology Reports, 30, e00623. https://doi.org/10.1016/j.btre.2021.e00623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Tan, R. X., & Zou, W. X. (2001). Endophytes: A rich source of functional metabolites. Natural Product Reports, 18(4), 448–459. https://doi.org/10.1039/b100918o

    Article  CAS  PubMed  Google Scholar 

  32. Germaine, K., Keogh, E., Garcia-Cabellos, G., Borremans, B., Lelie, D. V. D., Barac, T., Oeyen, L., Vangronsveld, J., Moore, F. P., Moore, E. R. B., Campbell, C. D., Ryan, D., & Dowling, D. N. (2004). Colonisation of poplar trees by gfp expressing bacterial endophytes. FEMS Microbiology Ecology, 48(1), 109–118. https://doi.org/10.1016/j.femsec.2003.12.009

    Article  CAS  PubMed  Google Scholar 

  33. Demers, M. J. M. (2022). Alternaria alternata as endophyte and pathogen. Microbiology, 168(3), 001153. https://doi.org/10.1099/mic.0.001153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lou, J. F., Fu, L. Y., Peng, Y. L., & Zhou, L. G. (2013). Metabolites from Alternaria fungi and their bioactivities. Molecules, 18(5), 5891–5935. https://doi.org/10.3390/molecules18055891

    Article  PubMed  PubMed Central  Google Scholar 

  35. Chen, J., Qiu, X., Wang, R., Duan, L., Chen, S., Luo, J., & Kong, L. (2009). Inhibition of human gastric carcinoma cell growth in vitro and in vivo by cladosporol isolated from the paclitaxel-producing strain Alternaria alternata var monosporus. Biological and Pharmaceutical Bulletin, 32(12), 2072–2074. https://doi.org/10.1248/bpb.32.2072

    Article  CAS  PubMed  Google Scholar 

  36. Andrade, H. F., Araújo, L. C. A., Santos, B. S. D., Paiva, P. M. G., Napoleão, T. H., Correia, M., Oliveira, M. B. M., Lima, G. M. S., Ximenes, R. M., Silva, T. D. D., Silva, G. R. D., & Silva, M. V. D. (2018). Screening of endophytic fungi stored in a culture collection for taxol production. Brazilian Journal of Microbiology, 49, 59–63. https://doi.org/10.1016/j.bjm.2018.06.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Tian, R. P., Yang, Q., Zhou, G. L., Tang, J. Q., Zhnag, L. Z., & Fang, C. X. (2006). Taxonomic study on a taxol producing fungus isolated from bark of Taxus chinensis var. mairei. Journal of Wuhan Botanical Research, 24(6), 541–545.

    CAS  Google Scholar 

  38. Bian, G., Yuan, Y., Tao, H., Shi, X., Zhong, X., Han, Y., Fu, S., Fang, C., Deng, Z., & Liu, T. (2017). Production of taxadiene by engineering of mevalonate pathway in Escherichia coli and endophytic fungus Alternaria alternata TPF6. Biotechnology Journal, 12(4), 1600697. https://doi.org/10.1002/biot.201600697

    Article  CAS  Google Scholar 

  39. Strobel, G. A., & Hess, W. M. (1997). Glucosylation of the peptide leucinostatin A, produced by an endophytic fungus of European yew, may protect the host from leucinostatin toxicity. Chemistry and Biology, 4(7), 529–536. https://doi.org/10.1016/s1074-5521(97)90325-2

    Article  CAS  PubMed  Google Scholar 

  40. El-Sayed, E. R., Zaki, A. G., Ahmed, A. S., & Ismaiel, A. A. (2020). Production of the anticancer drug taxol by the endophytic fungus Epicoccum nigrum TXB502: Enhanced production by gamma irradiation mutagenesis and immobilization technique. Applied Microbiology and Biotechnology, 104(16), 6991–7003. https://doi.org/10.1007/s00253-020-10712-x

    Article  CAS  PubMed  Google Scholar 

  41. Kennedy, M., & Krouse, D. (1999). Strategies for improving fermentation medium performance: A review. Journal of Industrial Microbiology and Biotechnology, 23, 456–475. https://doi.org/10.1038/sj.jim.2900755

    Article  CAS  Google Scholar 

  42. Kashyap, P., Sabu, A., Pandey, A., Szakacs, G., & Soccol, C. R. (2002). Extra-cellular l-glutaminase production by Zygosaccharomyces rouxii under solid-state fermentation. Process Biochemistry, 38(3), 307–312. https://doi.org/10.1016/S0032-9592(02)00060-2

    Article  CAS  Google Scholar 

  43. Dai, W. L., & Tao, W. Y. (2008). Preliminary study on fermentation conditions of taxol-producing endophytic fungus. Chemical Industry and Engineering Progress, 27(6), 883–886.

    CAS  Google Scholar 

  44. Jin, R., Kang, J. C., Wen, T. C., He, J., & Lei, B. X. (2011). A study on optimal fermentation of an endophytic fungus producing taxol. Mygosystema, 30(2), 235–241.

    CAS  Google Scholar 

  45. Ruiz-Sanchez, J., Flores-Bustamante, Z. R., Dendooven, L., Favela-Torres, E., Soca-Chafre, G., Galindez-Mayer, J., & Flores-Cotera, L. B. (2010). A comparative study of taxol production in liquid and solid-state fermentation with Nigrospora sp. a fungus isolated from Taxus globosa. Journal of Applied Microbiology, 109(6), 2144–2150. https://doi.org/10.1111/j.1365-2672.2010.04846.x

    Article  CAS  PubMed  Google Scholar 

  46. Sonaimuthu, V., Krishnamoorthy, S., & Johnpaul, M. (2010). Optimization of process parameters for improved production of taxol by a novel endophytic fungus Pestalotiopsis oxyanthi SVJM060 isolated from Taxus baccta. Journal of Biotechnology, 150, 471. https://doi.org/10.1016/j.jbiotec.2010.09.704

    Article  Google Scholar 

  47. Li, D., Fu, D., Zhang, Y., Ma, X., Gao, L., Wang, X., Zhou, D., & Zhao, K. (2017). Isolation, purification, and identification of taxol and related taxanes from taxol-producing fungus Aspergillus niger subsp taxi. Journal of Microbiology and Biotechnology, 27(8), 1379–1385. https://doi.org/10.4014/jmb.1701.01018

    Article  CAS  PubMed  Google Scholar 

  48. Liu, K., Ding, X., Deng, B., & Chen, W. (2009). Isolation and characterization of endophytic taxol-producing fungi from Taxus chinensis. Journal of Industrial Microbiology and Biotechnology, 36(9), 1171–1177. https://doi.org/10.1007/s10295-009-0598-8

    Article  CAS  PubMed  Google Scholar 

  49. Zhao, K., Ping, W., Li, Q., Hao, S., Zhao, L., Gao, T., & Zhou, D. (2009). Aspergillus niger var. taxi, a new species variant of taxol-producing fungus isolated from Taxus cuspidata in China. Journal of Applied Microbiology, 107(4), 1202–1207. https://doi.org/10.1111/j.1365-2672.2009.04305.x

    Article  CAS  PubMed  Google Scholar 

  50. Qiao, W. C., Ling, F., Yu, L., Huang, Y. F., & Wang, T. (2017). Enhancing taxol production in a novel endophytic fungus, Aspergillus aculeatinus Tax-6, isolated from Taxus chinensis var. mairei. Fungal Biology, 121(12), 1037–1044. https://doi.org/10.1016/j.funbio.2017.08.011

    Article  CAS  PubMed  Google Scholar 

  51. Kumaran, R. S., Muthumary, J., & Hur, B. K. (2008). Taxol from Phyllosticta citricarpa, a leaf spot fungus of the angiosperm Citrus medica. Journal of Bioscience and Bioengineering, 106(1), 103–106. https://doi.org/10.1263/jbb.106.103

    Article  CAS  PubMed  Google Scholar 

  52. Wang, Y. D., Wu, J. C., & Yuan, Y. J. (2007). Salicylic acid-induced taxol production and isopentenyl pyrophosphate biosynthesis in suspension cultures of Taxus chinensis var. mairei. Cell Biology International, 31(10), 1179–1183. https://doi.org/10.1016/j.cellbi.2007.03.038

    Article  CAS  PubMed  Google Scholar 

  53. Kumaran, R. S., Kim, H. J., & Hur, B. K. (2010). Taxol promising fungal endophyte, Pestalotiopsis species isolated from Taxus cuspidata. Journal of Bioscience and Bioengineering, 110(5), 541–546. https://doi.org/10.1016/j.jbiosc.2010.06.007

    Article  CAS  PubMed  Google Scholar 

  54. Plackett, R. L., & Burman, J. P. (1946). The design of optimum multifactorial experiments. Biometrika, 33, 305–325. https://doi.org/10.1093/biomet/33.4.305

    Article  Google Scholar 

  55. Box, G. E. P., & Behnken, D. W. (1960). Some new three level designs for the study of quantitative variables. Technometrics, 2, 455–475. https://doi.org/10.2307/1266454

    Article  Google Scholar 

  56. El-Sayed, E. R., & Zaki, A. G. (2023). Unlocking the biosynthetic potential of Penicillium roqueforti for hyperproduction of the immunosuppressant mycophenolic acid: Gamma radiation mutagenesis and response surface optimization of fermentation medium. Biotechnology and Applied Biochemistry, 70(1), 306–317. https://doi.org/10.1002/bab.2353

    Article  CAS  PubMed  Google Scholar 

  57. Garyali, S., Kumar, A., & Reddy, M. S. (2014). Enhancement of taxol production from endophytic fungus Fusarium redolens. Biotechnology and Bioprocess Engineering, 19(5), 908–915. https://doi.org/10.1007/s12257-014-0160-z

    Article  CAS  Google Scholar 

  58. Subban, K., Subramani, R., Srinivasan, V. P. M., Johnpaul, M., & Chelliah, J. (2019). Salicylic acid as an effective elicitor for improved taxol production in endophytic fungus Pestalotiopsis microspora. Plos One, 14(2), e0212736. https://doi.org/10.1371/journal.pone.0212736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Zhang, C. H., & Wu, J. Y. (2003). Ethylene inhibitors enhance elicitor-induced paclitaxel production in suspension cultures of Taxus spp. cells. Enzyme and Microbial Technology, 32(1), 71–77. https://doi.org/10.1016/s0141-0229(02)00266-1

    Article  CAS  Google Scholar 

  60. Zhao, K., Li, Z., Ge, N., Li, X., Wang, X., & Zhou, D. (2011). Investigation of fermentation conditions and optimization of medium for taxol production from taxol-producing fungi. Journal of Medicinal Plants Research, 5(29), 6528–6535. https://doi.org/10.5897/jmpr11.663

    Article  CAS  Google Scholar 

  61. El-Sayed, E. R., Ahmed, A. S., Hassan, I. A., Ismaiel, A. A., & El-Din, A. A. K. (2020). Semi-continuous production of the anticancer drug taxol by Aspergillus fumigatus and Alternaria tenuissima immobilized in calcium alginate beads. Bioprocess and Biosystems Engineering, 43(6), 997–1008. https://doi.org/10.1007/s00449-020-02295-8

    Article  CAS  PubMed  Google Scholar 

  62. El-Sayed, E. R., Ahmed, A. S., & Abdelhakim, H. K. (2020). A novel source of the cardiac glycoside digoxin from the endophytic fungus Epicoccum nigrum: Isolation, characterization, production enhancement by gamma irradiation mutagenesis and anticancer activity evaluation. Journal of Applied Microbiology, 128(3), 747–762. https://doi.org/10.1111/jam.14510

    Article  CAS  PubMed  Google Scholar 

  63. Ajikumar, P. K., Xiao, W. H., Tyo, K. E. J., Wang, Y., Simeon, F., Leonard, E., Mucha, O., Phon, T. H., Pfeifer, B., & Stephanopoulos, G. (2010). Isoprenoid pathway optimization for taxol precursor overproduction in Escherichia coli. Science, 330(6000), 70–74. https://doi.org/10.1126/science.1191652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We are very grateful to Liquid Chromatography Mass Spectrometry (LC-MS) Facility at Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University. The authors are grateful to the reviewers for the constructive comments.

Funding

This work was supported by Open Grant for Key Laboratory of Sustainable Forest Ecosystem Management (Northeast Forestry University), Ministry of Education (KFJJ2021YB01), Heilongjiang Provincial Natural Science Foundation of Joint Guidance Project (LH2021C015), National Natural Science Foundation of China for Key Program (31930076), the 111 Project of China (B20088), and the Heilongjiang Touyan Innovation Team Program (Tree Genetics and Breeding Innovation Team).

Author information

Authors and Affiliations

Authors

Contributions

Yuefeng Fu, Xinyue Li, and Xiaohan Yuan wrote the main manuscript text. Zhihui Zhang performed the experiments. Wei Wei and Cheng Xu analyzed the data. Jinfeng Song and Chengbo Gu conceived and designed the experiments. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Jinfeng Song or Chengbo Gu.

Ethics declarations

Ethics Approval

The present article does not involve any human and animal participation in experiments performed by authors. Therefore, no formal consent is needed.

Consent to Participate

This is not applicable because this study does not involve human participants.

Consent for Publication

This is not applicable because this study does not involve human participants.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 16 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fu, Y., Li, X., Yuan, X. et al. Alternaria alternata F3, a Novel Taxol-Producing Endophytic Fungus Isolated from the Fruits of Taxus cuspidata: Isolation, Characterization, Taxol Yield Improvement, and Antitumor Activity. Appl Biochem Biotechnol 196, 2246–2269 (2024). https://doi.org/10.1007/s12010-023-04661-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-023-04661-0

Keywords

Navigation