Skip to main content
SpringerLink
Log in

Improvement of fumigaclavine C production in a two-stage culture of Aspergillus fumigatus with molasses as a cost-effective ingredient

  • Research Paper
  • Published:
Biotechnology and Bioprocess Engineering Aims and scope Submit manuscript

Abstract

Fumigaclavine C (FC), which is produced by Aspergillus fumigatus, is a conidiation-associated ergot alkaloid with significant medical benefits. However, its application is restricted by low yields from submerged cultures. In this study, the technical feasibility of using molasses as a cost-effective ingredient for FC production in a two-stage culture of A. fumigatus was evaluated. The results indicated that molasses supplementation significantly enhanced FC accumulation by promoting conidiation and up-regulating hydroxymethylglutaryl-CoA reductase activity. Via the optimization of the two-stage process in the presence of molasses, FC production in shake flasks reached 226.9 mg/L, which was approximately three times that in the original medium (75.9 mg/L). The use of molasses as a cost-effective ingredient for FC fermentation was also successfully reproduced in a lab-scale bioreactor system in which the maximum FC production reached 215.0 mg/L. The FC production obtained in this study is the highest ever reported. This increased efficiency will enable large-scale production of FC and extend the application of molasses as a low-cost substrate for producing other conidiation-related secondary metabolites.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jakubczyk, D., J. Z. Cheng, and S. E. O’Connor (2014) Biosynthesis of the ergot alkaloids. Nat. Prod. Rep. 31: 1328–1338.

    Article  CAS  Google Scholar 

  2. Wu, X. F., M. J. Fei, R. G. Shu, R. X. Tan, and Q. Xu (2005) Fumigaclavine C, an fungal metabolite, improves experimental colitis in mice via downregulating Th1 cytokine production and matrix metalloproteinase activity. Int. Immunopharmacol. 5: 1543–1553.

    Article  CAS  Google Scholar 

  3. Zhao, Y., J.Y. Liu, J. Wang, L. Wang, H. Yin, R.X. Tan and Q. Xu (2004) Fumigaclavine C improves concanavalin A-induced liver injury in mice mainly via inhibiting TNF-alpha production and lymphocyte adhesion to extracellular matrices. J. Pharm. Pharmacol. 56: 775–782.

    Article  CAS  Google Scholar 

  4. Du, R. H., E. G. Li, Y. Cao, Y. C. Song, and R. X. Tan (2011) Fumigaclavine C inhibits tumor necrosis factor á production via suppression of toll-like receptor 4 and nuclear factor êB activation in macrophages. Life Sci. 89: 235–240.

    Article  CAS  Google Scholar 

  5. Li, Y. X., S. W. A. Himaya, P. Dewapriya, C. Zhang, and S. K. Kim (2013) Fumigaclavine C from a marine-derived fungus Aspergillus fumigatus induces apoptosis in MCF-7 breast cancer cells. Mar. Drug. 11: 5063–5086.

    Article  CAS  Google Scholar 

  6. Du, R. H., S. Y. Qin, L. S. Shi, Z. Q. Zhou, X. Y. Zhu, J. Liu, R. X. Tan, and W. Cao (2014) Fumigaclavine C activates PPARγ pathway and attenuates atherogenesis in ApoE-deficient mice. Atherosclerosi. 234: 120–128.

    Article  CAS  Google Scholar 

  7. Panaccione, D. G. and C. M. Coyle (2005) Abundant respirable ergot alkaloids from the common airborne fungus Aspergillus fumigatus. Appl. Environ. Microb. 71: 3106–3111.

    Article  CAS  Google Scholar 

  8. Coyle, C. M., S. C. Kenaley, W. R. Rittenour, and D. G. Panaccione (2007) Association of ergot alkaloids with conidiation in Aspergillus fumigatus. Mycol. 99: 804–811.

    Article  CAS  Google Scholar 

  9. Mulinti, P., N.A. Allen, C. M. Coyle, F. N. Gravelat, D. C. Sheppard, and D. G. Panaccione (2014) Accumulation of ergot alkaloids during conidiophore development in Aspergillus fumigatus. Curr. Microbiol. 68: 1–5.

    Article  CAS  Google Scholar 

  10. Wu, Q., Y. Song, H. Xu, Y. Guo, J. Li, and R. X. Tan (2012) Medium optimization for enhanced co-production of two bioactive metabolites in the same fermentation by a statistical approach. J. Asian Nat. Prod. Res. 13: 37–41.

    Google Scholar 

  11. Zhu, Y. X., L. Y. Yao, R. H. Jiao, Y. H. Lu, and R. X. Tan (2014) Enhanced production of Fumigaclavine C in liquid culture of Aspergillus fumigatus under a two-stage process. Bioresour. Technol. 152: 162–168.

    Article  CAS  Google Scholar 

  12. Yao, L.Y., Y. X. Zhu, R. H. Jiao, Y. H. Lu, and R. X. Tan (2014) Enhanced production of fumigaclavine C by ultrasound stimulation in a two-stage culture of Aspergillus fumigatus CY018. Bioresour. Technol. 159: 112–117.

    Article  CAS  Google Scholar 

  13. Xu, K. and P. Xu (2014) Efficient production of l-lactic acid using co-feeding strategy based on cane molasses/glucose carbon sources. Bioresour. Technol. 153: 23–29.

    Article  CAS  Google Scholar 

  14. Arshad, M., S. Ahmed, M. A. Zia, and M. I. Rajoka (2014) Kinetics and thermodynamics of ethanol production by Saccharomyces cerevisiae MLD10 using molasses. Appl. Biochem. Biotechnol. 172: 2455–2464.

    Article  CAS  Google Scholar 

  15. Cazetta, M. L., M. A. P. C. Celligoi, J. B. Buzato, and I. S. Scarmino (2007) Fermentation of molasses by Zymomonas mobilis: Effects of temperature and sugar concentration on ethanol production. Bioresour. Technol. 98: 2824–2828.

    Article  CAS  Google Scholar 

  16. Wee, Y. J., J. N. Kim, J. S. Yun, and H. W. Ryu (2004) Utilization of sugar molasses for economical L(+)-lactic acid production by batch fermentation of Enterococcus faecalis. Enz. Microb. Technol. 35: 568–573.

    Article  CAS  Google Scholar 

  17. Wang, J. L., X. H. Wen, and D. Zhou (2000) Production of citric acid from molasses integrated with in-situ product separation by ion-exchange resin adsorption. Bioresour. Technol. 75: 231–234.

    Article  Google Scholar 

  18. Lee, S. M., B. R. Oh, J. M. Park, A. Yu, S. Y. Heo, W. K. Hong, J. W. Seo, and C. H. Kim (2014) Optimized production of 2,3-butanediol by a lactate dehydrogenase-deficient mutant of Klebsiella pneumoniae. Biotechnol. Bioproc. Eng. 18: 1210–1215.

    Article  CAS  Google Scholar 

  19. Park, K. M., M. W. Song, and J. H. Lee (2008) Production of carotenoids by ß-ionone-resistant mutant of Xanthophyllomyces dendrorhous using various carbon sources. Biotechnol. Bioproc. Eng. 13: 197–203.

    Article  CAS  Google Scholar 

  20. López, J., J. M. Naranjo, J. Higuita, M. Cubitto, C. Cardona, and M. Villar (2012) Biosynthesis of PHB from a new isolated Bacillus megaterium strain: Outlook on future developments with endospore forming bacteria. Biotechnol. Bioproc. Eng. 17: 250–258.

    Article  CAS  Google Scholar 

  21. Lee, Y., M. J. Lee, Y. E. Choi, G. T. Chun, and Y. S. Jeong (2015) Optimization of cultivation medium and fermentation parameters for lincomycin production by Streptomyces lincolnensis. Biotechnol. Bioproc. Eng. 19: 1014–1021.

    Article  CAS  Google Scholar 

  22. Chang, P. K. and S. S. T. Hua (2007) Molasses supplementation promotes conidiation but suppresses aflatoxin production by small sclerotial Aspergillus flavus. Lett. Appl. Microbiol. 44: 131–137.

    Article  CAS  Google Scholar 

  23. Blankenship, J. D., M. J. Spiering, H. H. Wilkinson, F. F. Fannin, L. P. Bush, and C. L. Schardl (2001) Production of loline alkaloids by the grass endophyte, Neotyphodium uncinatum, in defined media. Phytochem. 58: 395–401.

    Article  CAS  Google Scholar 

  24. Boichenko, L.V., N. F. Zelenkova, M. U. Arinbasarov, and R. T. A. Reshetilova (2003) Optimization of conditions for storage and cultivation of the fungus Claviceps sp., a producer of the ergot alkaloid agroclavine. Appl. Biochem. Microbiol. 39: 335–340.

    Article  CAS  Google Scholar 

  25. Shasaltaneh, M. D., J. Fooladi, and S. Z. Moosavi-Nejad (2010) L-tryptophan production by Escherichia coli in the presence of Iranian cane molasses. J. Paramed. Sci. 1: 19–25.

    Google Scholar 

  26. Wallwey, C. and S. M. Li (2011) Ergot alkaloids: structure diversity, biosynthetic gene clusters and functional proof of biosynthetic genes. Nat. Prod. Rep. 28: 496–510.

    Article  CAS  Google Scholar 

  27. Liu, J., J. Huang, Y. Jiang, and F. Chen (2012) Molasses-based growth and production of oil and astaxanthin by Chlorella zofingiensis. Bioresour. Technol. 107: 393–398.

    Article  CAS  Google Scholar 

  28. Hatano, K. I., S. Kikuchi, Y. Nakamura, H. Sakamoto, M. Takigami, and Y. Kojima (2009) Novel strategy using an adsorbentcolumn chromatography for effective ethanol production from sugarcane or sugar beet molasses. Bioresour. Technol. 100: 4697–4703.

    Article  CAS  Google Scholar 

  29. Xia, J., Z. Xu, H. Xu, J. Liang, S. Li, and X. Feng (2014) Economical production of poly(ε-l-lysine) and poly(l-diaminopropionic acid) using cane molasses and hydrolysate of streptomyces cells by Streptomyces albulus PD-1. Bioresour. Technol. 164: 241–247.

    Article  CAS  Google Scholar 

  30. Liu, Y. P., P. Zheng, Z. H. Sun, Y. Ni, J. J. Dong, and L. L. Zhu (2008) Economical succinic acid production from cane molasses by Actinobacillus succinogenes. Bioresour. Technol. 99: 1736–1742.

    Article  CAS  Google Scholar 

  31. Wang, G. and J. D. Keasling (2002) Amplification of HMG-CoA reductase production enhances carotenoid accumulation in Neurospora crassa. Metab. Eng. 201: 193–201.

    Article  CAS  Google Scholar 

  32. Adams, T. H., J. K. Wieser, and J. H. Yu (1998) Asexual sporulation in Aspergillus nidulans. Microbiol. Mol. Biol. R. 62: 35–54.

    CAS  Google Scholar 

  33. Morton, A. G. (1961) The induction of sporulation in mould fungi. Proc. R. Soc. Lond. 153: 548–569.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, China

    Yi-Xiang Zhu, Wei-Wei Hu, Ling-Yun Yao, Wan-Guo Yu & Yan-Hua Lu

  2. Shanghai Collaborative Innovation Center for Biomanufacturing Technology, East China University of Science and Technology, 130 Meilong Road, Shanghai, China

    Yi-Xiang Zhu, Wei-Wei Hu, Ling-Yun Yao, Wan-Guo Yu & Yan-Hua Lu

  3. Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China

    Rui-Hua Jiao & Ren-Xiang Tan

Authors
  1. Yi-Xiang Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei-Wei Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ling-Yun Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wan-Guo Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rui-Hua Jiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yan-Hua Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ren-Xiang Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yan-Hua Lu or Ren-Xiang Tan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhu, YX., Hu, WW., Yao, LY. et al. Improvement of fumigaclavine C production in a two-stage culture of Aspergillus fumigatus with molasses as a cost-effective ingredient. Biotechnol Bioproc E 20, 1106–1113 (2015). https://doi.org/10.1007/s12257-015-0193-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12257-015-0193-y

Keywords

Search

Navigation