Skip to main content
SpringerLink
Log in

Production of Mycophenolic Acid by Penicillium brevicompactum Using Solid State Fermentation

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

Abstract

Solid-state fermentation using the microfungus Penicillium brevicompactum for the production of mycophenolic acid is reported in this paper. Of the initial substrates tested (whole wheat, cracked wheat, long grain Basmati rice, and short grain Parmal rice), Parmal rice proved to be the best. Under initial conditions, using steamed Parmal rice with 80% (w/w) initial moisture content, a maximum mycophenolic acid concentration of 3.4 g/kg substrate was achieved in 12 days of fermentation at 25 °C. The above substrate was supplemented with the following additional nutrients (g/L packed substrate): glucose 40.0, peptone 54.0, KH2PO4 8.0, MgSO4⋅7H2O 2.0, glycine 7.0, and methionine 1.65 (initial pH 5.0). A small amount of a specified trace element solution was also added. The final mycophenolic acid concentration was increased to nearly 4 g/kg substrate by replacing glucose with molasses. Replacing Parmal rice with rice bran as substrate further improved the mycophenolic acid production to nearly 4.5 g/kg substrate.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Ismaiel, A. A., Ahmed, A. S., & El-Sayed, E.-S. R. (2014). Optimization of submerged fermentation conditions for immunosuppressant mycophenolic acid production by Penicillium roqueforti isolated from blue-molded cheeses: enhanced production by ultraviolet and gamma irradiation. World Journal of Microbiology and Biotechnology, 30(10), 2625–2638.

    Article  CAS  Google Scholar 

  2. Ardestani, F., Fatemi, S. S. A., Yakhchali, B., Hosseyni, S. M., & Najafpour, G. (2010). Evaluation of mycophenolic acid production by Penicillium brevicompactum MUCL 19011 in batch and continuous submerged cultures. Biochemical Engineering Journal, 50(3), 99–103.

    Article  CAS  Google Scholar 

  3. Xie, X., Jiang, Y., Lai, X., Xiang, S., Shou, Z., Chen, J., & Rizzari, M. (2015). mTOR inhibitor versus mycophenolic acid as the primary immunosuppression regime combined with calcineurin inhibitor for kidney transplant recipients: a meta-analysis. BMC Nephrology, 16(1), 91.

    Article  Google Scholar 

  4. Yoo, C. G., Nghiem, N. P., Hicks, K. B., & Kim, T. H. (2013). Maximum production of fermentable sugars from barley straw using optimized soaking in aqueous ammonia (SAA) pretreatment. Applied Biochemistry and Biotechnology, 169(8), 2430–2441.

    Article  CAS  Google Scholar 

  5. Abd Rahman, A. N., Tett, S. E., & Staatz, C. E. (2013). Clinical pharmacokinetics and pharmacodynamics of mycophenolate in patients with autoimmune disease. Clinical Pharmacokinetics, 52(5), 303–331.

    Article  CAS  Google Scholar 

  6. Davidson, A., & Diamond, B. (2001). Autoimmune diseases. The New England Journal of Medicine, 345(5), 340–350.

    Article  CAS  Google Scholar 

  7. De Winter, B. C. M., & Van Gelder, T. (2008). Therapeutic drug monitoring for mycophenolic acid in patients with autoimmune diseases. Nephrology, Dialysis, Transplantation, 1(3).

  8. Séguin, V., Gente, S., Heutte, N., Vérité, P., Kientz-Bouchart, V., Sage, L., & Garon, D. (2014). First report of mycophenolic acid production by Eurotium repens isolated from agricultural and indoor environments. World Mycotoxin Journal, 7(3), 321–328.

    Article  Google Scholar 

  9. Xu, Z. N., & Yang, S. T. (2007). Production of mycophenolic acid by Penicillium brevicompactum immobilized in a rotating fibrous-bed bioreactor. Enzyme and Microbial Technology, 40(4), 623–628.

    Article  CAS  Google Scholar 

  10. Dong, Y., Xu, R., Wang, L., Zhang, J., Bai, C., Sun, A., & Wei, D. (2015). A combined feeding strategy for enhancing mycophenolic acid production by fed-batch fermentation in Penicillium brevicompactum. Process Biochemistry, 50(3), 336–340.

    Article  CAS  Google Scholar 

  11. Alani, F., Grove, J. A., Anderson, W. A., & Moo-Young, M. (2009). Mycophenolic acid production in solid-state fermentation using a packed-bed bioreactor. Biochemical Engineering Journal, 44(2–3), 106–110.

    Article  CAS  Google Scholar 

  12. Sadhukhan, A. K., Ramana Murthy, M. V., Ajaya Kumar, R., Mohan, E. V. S., Vandana, G., Bhar, C., & Venkateswara Rao, K. (1999). Optimization of mycophenolic acid production in solid state fermentation using response surface methodology. Journal of Industrial Microbiology & Biotechnology, 22, 33–38.

    Article  CAS  Google Scholar 

  13. Nigam, P., & Singh, D. (1994). Solid-state (substrate) fermentation systems and their applications in biotechnology. Journal of Basic Microbiology, 34(6), 405–423.

    Article  CAS  Google Scholar 

  14. Pandey, A., Soccol, C. R., & Mitchell, D. (2000). New developments in solid state fermentation: I-bioprocesses and products. Process Biochemistry, 35(10), 1153–1169.

    Article  CAS  Google Scholar 

  15. Gombert, A. K., Pinto, A. L., Castilho, L. R., & Freire, D. M. G. (1999). Lipase production by Penicillium restrictum in solid-state fermentation using babassu oil cake as substrate. Process Biochemistry, 35(1–2), 85–90.

    Article  CAS  Google Scholar 

  16. Raimbault, M. (1998). General and microbiological aspects of solid substrate fermentation. Electronic Journal of Biotechnology, 1(2), 174–188.

    Article  Google Scholar 

  17. Muller dos Santos, M., Souza da Rosa, A., Dal’Boit, S., Mitchell, D. A., & Krieger, N. (2004). Thermal denaturation: is solid-state fermentation really a good technology for the production of enzymes? Bioresource Technology, 93(3), 261–268.

    Article  CAS  Google Scholar 

  18. Dhillon, G. S., Brar, S. K., Verma, M., & Tyagi, R. D. (2011). Enhanced solid-state citric acid bio-production using apple pomace waste through surface response methodology. Journal of Applied Microbiology, 110(4), 1045–1055.

    Article  CAS  Google Scholar 

  19. Chen, H. (2013). Introduction. In Modern solid state fermentation (pp. 1–21). Dordrecht: Springer Netherlands.

    Chapter  Google Scholar 

  20. Angel-Cuapio, A., Figueroa-Montero, A., Favela-Torres, E., Viniegra-Gonzlez, G., Perraud-Gaime, I., & Loera, O. (2015). Critical values of porosity in rice cultures of Isaria fumosorosea by adding water hyacinth: effect on conidial yields and quality. Applied Biochemistry and Biotechnology, 177(2), 446–457.

    Article  CAS  Google Scholar 

  21. Pandey, A., Ashakumary, L., Selvakumar, P., & Vijayalakshmi, K. S. (1994). Influence of water activity on growth and activity of Aspergillus niger for glycoamylase production in solid-state fermentation. World Journal of Microbiology & Biotechnology, 10(4), 485–486.

    Article  CAS  Google Scholar 

  22. Bakri, Y., Jacques, P., & Thonart, P. (2003). Xylanase production by Penicillium canescens 10-10c in solid-state fermentation. Applied Biochemistry and Biotechnology, 108(1), 737–748.

    Article  Google Scholar 

  23. Torrado, A. M., Cortés, S., Manuel Salgado, J., Max, B., Rodríguez, N., Bibbins, B. P., & Manuel Domínguez, J. (2011). Citric acid production from orange peel wastes by solid-state fermentation. Brazilian journal of microbiology: [publication of the Brazilian Society for Microbiology], 42(1), 394–409.

    Article  CAS  Google Scholar 

  24. Chen, H. (2013). Aerobic solid-state fermentation. In Modern solid state fermentation (pp. 141–197). Dordrecht: Springer Netherlands.

    Chapter  Google Scholar 

  25. Shaligram, N. S., Singh, S. K., Singhal, R. S., Pandey, A., & Szakacs, G. (2009). Compactin production studies using Penicillium brevicompactum under solid-state fermentation conditions. Applied Biochemistry and Biotechnology, 159(2), 505–520.

    Article  CAS  Google Scholar 

  26. Viccini, G., Mannich, M., Maria, D., Capalbo, F., Valdebenito-Sanhueza, R., & Mitchell, D. A. (2007). Spore production in solid-state fermentation of rice by Clonostachys rosea, a biopesticide for gray mold of strawberries. Process Biochemistry, 42, 275–278.

    Article  CAS  Google Scholar 

  27. Patel, G., Patil, M. D., Soni, S., Khobragade, T. P., Chisti, Y., & Banerjee, U. C. (2016). Production of mycophenolic acid by Penicillium brevicompactum—a comparison of two methods of optimization. Biotechnology Reports, 11, 77–85.

    Article  Google Scholar 

  28. Prabhu, S., Sharma, P. D., Tiwari, S., Melarkode, R., Gururaja, R., & Suryanarayan, S. (2004). Process for producing mycophenolic acid using Penicillium arenicola BICC 7673. U.S. Patent no. 2008/0227164 A1.

  29. Patil, M. D., Shinde, K. D., Patel, G., Chisti, Y., & Banerjee, U. C. (2016). Use of response surface method for maximizing the production of arginine deiminase by Pseudomonas putida. Biotechnology Reports, 10, 29–37.

    Article  Google Scholar 

  30. Cai, Y., Liang, X., Liao, X., Ding, Y., Sun, J., & Li, X. (2010). High-yield hypocrellin a production in solid-state fermentation by Shiraia sp. SUPER-H168. Applied Biochemistry and Biotechnology, 160(8), 2275–2286.

    Article  CAS  Google Scholar 

  31. Revankar, M. S., Desai, K. M., & Lele, S. S. (2007). Solid-state fermentation for enhanced production of laccase using indigenously isolated Ganoderma sp. Applied Biochemistry and Biotechnology, 143(1), 16–26.

    Article  CAS  Google Scholar 

  32. Patil, M. D., Patel, G., Surywanshi, B., Shaikh, N., Garg, P., & Chisti, Y. (2016). Disruption of Pseudomonas putida by high pressure homogenization: a comparison of the predictive capacity of three process models for the efficient release of arginine deiminase. AMB Express, 6, 84.

    Article  Google Scholar 

  33. El-Naggar, M. Y., El-Assar, S. A., & Abdul-Gawad, S. M. (2009). Solid-state fermentation for the production of meroparamycin by Streptomyces sp. strain MAR01. Journal of Microbiology and Biotechnology, 19(5), 468–473.

    Article  CAS  Google Scholar 

  34. Hymery, N., Vasseur, V., Coton, M., Mounier, J., Jany, J. L., Barbier, G., & Coton, E. (2014). Filamentous fungi and mycotoxins in cheese: a review. Comprehensive Reviews in Food Science and Food Safety, 13(4), 437–456.

    Article  CAS  Google Scholar 

  35. Niu, X., Qiu, S., Wu, Y., Yuan, J., & Xu, Y. (2011). Highly effective extraction of oil from soybean by pretreatment of solid-state fermentation with fungi. Frontiers of Chemical Science and Engineering, 5(1), 122–125.

    Article  CAS  Google Scholar 

  36. De Castro, A. M., De Andréa, T. V., Dos Reis Castilho, L., & Freire, D. M. G. (2010). Use of mesophilic fungal amylases produced by solid-state fermentation in the cold hydrolysis of raw babassu cake starch. Applied Biochemistry and Biotechnology, 162(6), 1612–1625.

    Article  Google Scholar 

  37. Silva, D., Tokuioshi, K., Martins, E. D. S., Da Silva, R., & Gomes, E. (2005). Production of pectinase by solid-state fermentation with Penicillium viridicatum RFC3. Process Biochemistry, 40(8), 2885–2889.

    Article  CAS  Google Scholar 

  38. Aggelopoulos, T., Bekatorou, A., Pandey, A., Kanellaki, M., & Koutinas, A. A. (2013). Discarded oranges and brewer’s spent grains as promoting ingredients for microbial growth by submerged and solid state fermentation of agro-industrial waste mixtures. Applied Biochemistry and Biotechnology, 170(8), 1885–1895.

    Article  CAS  Google Scholar 

  39. Veana, F., Martínez-Hernández, J. L., Aguilar, C. N., Rodríguez-Herrera, R., & Michelena, G. (2014). Utilization of molasses and sugar cane bagasse for production of fungal invertase in solid state fermentation using Aspergillus niger GH1. Brazilian journal of microbiology: [publication of the Brazilian Society for Microbiology], 45(2), 373–377.

    Article  CAS  Google Scholar 

  40. Banat, I. M., Satpute, S. K., Cameotra, S. S., Patil, R., Nyayanit, N. V, & Spano, G. (2014). Cost effective technologies and renewable substrates for biosurfactants’ production. Frontier in Microbiology, 5, 1–81.

  41. Awad, G. E. A., Helal, M. M. I., Danial, E. N., & Esawy, M. A. (2014). Optimization of phytase production by Penicillium purpurogenum GE1 under solid state fermentation by using Box-Behnken design. Saudi Journal of Biological Sciences, 21(1), 81–88.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

GP and MP gratefully acknowledge the Department of Biotechnology (DBT), New Delhi, India for the award of Senior Research Fellowship. SS gratefully acknowledges the Department of Science and Technology (DST), New Delhi, India for the award of DST-INSPIRE fellowship.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Technology (Biotechnology), National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab, 160062, India

    Gopal Patel, Mahesh D. Patil, Surbhi Soni & Uttam Chand Banerjee

  2. School of Engineering, Massey University, Private Bag, Palmerston North, 11 222, New Zealand

    Yusuf Chisti

Authors
  1. Gopal Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mahesh D. Patil
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Surbhi Soni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yusuf Chisti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Uttam Chand Banerjee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Uttam Chand Banerjee.

Ethics declarations

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Patel, G., Patil, M.D., Soni, S. et al. Production of Mycophenolic Acid by Penicillium brevicompactum Using Solid State Fermentation. Appl Biochem Biotechnol 182, 97–109 (2017). https://doi.org/10.1007/s12010-016-2313-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-016-2313-3

Keywords

Search

Navigation