Applied Biochemistry and Biotechnology

, Volume 186, Issue 2, pp 496–506 | Cite as

Efficient Biotransformation of Phytosterols to Dehydroepiandrosterone by Mycobacterium sp.

  • Pei Zhou
  • Ya-kun Fang
  • Hao-ke Yao
  • Hua Li
  • Gang Wang
  • Yu-peng Liu


In this study, a method for the efficient production of dehydroepiandrosterone (DHEA) from phytosterols in a vegetable oil/aqueous two-phase system by Mycobacterium sp. was developed. After the 3-hydroxyl group of phytosterols was protected, they could be converted into DHEA with high yield and productivity by Mycobacterium sp. NRRL B-3683. In a shake flask biotransformation, 15.05 g l−1 of DHEA and a DHEA yield of 85.39% (mol mol−1) were attained after 7 days with an initial substrate concentration of 25 g l−1. When biotransformation was carried out in a 30-l stirred bioreactor with 25 g l−1 substrate, the DHEA concentration and yield was 16.33 g l−1 and 92.65% (mol mol−1) after 7 days, respectively. The results of this study suggest that inexpensive phytosterols could be utilized for the efficient production of DHEA.


Phytosterols Dehydroepiandrosterone Oil/aqueous two-phase system biotransformation Mycobacterium 


Funding Information

This research was supported by grants from the Key Project of Science and Technology of Henan Province (No. 152102210255) and the Foundation for University Young Back-bone Teachers of Henan Province (No. 2014GGJS-157).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Zuidena, M., Haverkorta, S. Q., Tan, Z., Daamsc, J., Loka, A., & Olffad, M. (2017). DHEA and DHEA-S levels in posttraumatic stress disorder: a meta-analytic review. Psychoneuroendocrinology, 84, 76–82.CrossRefGoogle Scholar
  2. 2.
    Mascotti, M. L., Palazzolo, M. A., Bisogno, F. R., & Kurina-Sanz, M. (2016). Biotransformation of dehydro-epi-androsterone by Aspergillus parasiticus: metabolic evidences of BVMO activity. Steroids, 109, 44–49.CrossRefGoogle Scholar
  3. 3.
    Stárka, L., Dušková, M., & Hill, M. (2015). Dehydroepiandrosterone: a neuroactive steroid. The Journal of Steroid Biochemistry and Molecular Biology, 145, 254–260.CrossRefGoogle Scholar
  4. 4.
    Shealy, C. N. (1995). A review of dehydroepiandrosterone (DHEA). Integrative Physiological and Behavioral Science, 30(4), 308–313.CrossRefGoogle Scholar
  5. 5.
    Campi, B., Frascarelli, S., Pietri, E., Massa, I., Donati, C., Bozic, R., Bertelloni, S., Paolicchi, A., Zucchi, R., & Saba, A. (2018). Quantification of dehydroepiandrosterone in human serum on a routine basis: development and validation of a tandem mass spectrometry method based on a surrogate analyte. Analytical and Bioanalytical Chemistry, 410(2), 407–416.CrossRefGoogle Scholar
  6. 6.
    Garrido, M., Bratoeff, E., Garcia-Lorenzana, M., Heuze, Y., Soriano, J., Valencia, N., Cortes, F., & Cabeza, M. (2013). Biological evaluation of androstene derivatives. Archiv der Pharmazie, 346(1), 62–70.CrossRefGoogle Scholar
  7. 7.
    Tong, W. Y., & Dong, X. (2009). Microbial biotransformation: recent developments on steroid drugs. Recent Patents on Biotechnology, 3(2), 141–153.CrossRefGoogle Scholar
  8. 8.
    Bahrke, M. S., & Yesalis, C. E. (2004). Abuse of anabolic androgenic steroids and related substances in sport and exercise. Current Opinion in Pharmacology, 4(6), 614–620.CrossRefGoogle Scholar
  9. 9.
    Pan, G. F., He, Y. J., & Xi, Z. B. (2014). Synthesis of dehydroepiandrosterone. [in Chinese] Guangdong Chemical Industry 41(12):70–70.Google Scholar
  10. 10.
    Tamao, K., Nakajima, T., Sumiya, R., Arai, H., Higuchi, N., & Ito, Y. (1986). Stereocontrol in intramolecular hydrosilylation of allyl and homoallyl alcohols: a new approach to the stereoselective synthesis of 1, 3-diol skeletons. Journal of the American Chemical Society, 108(19), 6090–6093.CrossRefGoogle Scholar
  11. 11.
    Shen, L. Q., Zuo, Q. J., & Lei, H. F. (2011). A synthetical method of dehydroepiandrosterone. [in Chinese] Chinese Patent 201110085711.X.Google Scholar
  12. 12.
    Bhatti, H. N., & Khera, R. A. (2012). Biological transformations of steroidal compounds: a review. Steroids, 77(12), 1267–1290.CrossRefGoogle Scholar
  13. 13.
    Fernandes, P., Cruz, A., Angelova, B., Pinheiro, H., & Cabral, J. (2003). Microbial conversion of steroid compounds: recent developments. Enzyme and Microbial Technology, 32(6), 688–705.CrossRefGoogle Scholar
  14. 14.
    Witholt, B. (2001). Industrial biocatalysis today and tomorrow. Nature, 409, 258–268 Tischer.CrossRefGoogle Scholar
  15. 15.
    Andrushina, V., Druzhinina, A., Yaderets, V., Stitsenko, T., & Voishvillo, N. (2011). Hydroxylation of steroids by Curvularia lunata mycelium in the presence of methyl-β-cyclodextrine. Applied Biochemistry and Microbiology, 47(1), 42–48.CrossRefGoogle Scholar
  16. 16.
    Perez, C., Falero, A., Hung, B. R., Tirado, S., & Balcinde, Y. (2005). Bioconversion of phytosterols to androstanes by Mycobacteria growing on sugar cane mud. Journal of Industrial Microbiology & Biotechnology, 32(3), 83–86.CrossRefGoogle Scholar
  17. 17.
    Donova, M. V., Dovbnya, D. V., Sukhodolskaya, G. V., Khomutov, S. M., Nikolayeva, V. M., Kwon, I., & Han, K. (2005). Microbial conversion of sterol-containing soybean oil production waste. Journal of Chemical Technology and Biotechnology, 80(1), 55–60.CrossRefGoogle Scholar
  18. 18.
    Malaviya, A., & Gomes, J. (2008). Androstenedione production by biotransformation of phytosterols. Bioresource Technology, 99(15), 6725–6737.CrossRefGoogle Scholar
  19. 19.
    Liu, X. Q., Meng, H., & Yang, K. A. (2012). preparation method of dehydroepiandrosterone by microbial fermentation. [in Chinese] Chinese Patent 201210316197.0.Google Scholar
  20. 20.
    Donova, M. V. (2007). Transformation of steroids by actinobacteria: a review. Applied Biochemistry and Microbiology, 43, 5–18.CrossRefGoogle Scholar
  21. 21.
    Granot, I., Aharonowitz, Y., & Freeman, A. (1988). Cosolvent effect on Δ 1-steroid-reductase activity of free and PAAH entrapped Mycobacterium sp. NRRL B-3805 cells. Applied Microbiology and Biotechnology, 27(5-6), 457–463.CrossRefGoogle Scholar
  22. 22.
    Ahmad, S., & Johri, B. (1993). Microbial transformation of sterols in organic media. Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 32, 67–69.Google Scholar
  23. 23.
    Flygare, S., & Larsson, P. O. (1989). Steroid transformation in aqueous two-phase systems: side-chain degradation of cholesterol by Mycobacterium sp. Enzyme and Microbial Technology, 11(11), 752–759.CrossRefGoogle Scholar
  24. 24.
    Wang, Z. F., Huang, Y. L., Rathman, J. F., & Yang, S. T. (2002). Lecithin-enhanced biotransformation of cholesterol to androsta-1,4-diene-3,17-dione and androsta-4-ene-3,17-dione. Journal of Chemical Technology and Biotechnology, 77(12), 1349–1357.CrossRefGoogle Scholar
  25. 25.
    Marsheck, W. J., Kraychy, S., & Muir, R. (1972). Microbial degradation of sterols. Applied Microbiology, 23(1), 72–77.Google Scholar
  26. 26.
    Zang, L., Jing, K. Q., & Liu, Y. P. (2015). Establishment of a method for the detection of dehydroepiandrosterone by microbial fermentation. [in Chinese]. Food and Fermentation Industries, 41(1), 216–219.Google Scholar
  27. 27.
    Xu, Y. G., Guan, Y. X., Wang, H. Q., & Yao, S. J. (2014). Microbial side-chain cleavage of phytosterols by mycobacteria in vegetable oil/aqueous two-phase system. Applied Biochemistry and Biotechnology, 174(2), 522–533.CrossRefGoogle Scholar
  28. 28.
    Faller, M., Niederweis, M., & Schulz, G. E. (2004). The structure of a mycobacterial outer-membrane channel. Science, 303(5661), 1189–1192.CrossRefGoogle Scholar
  29. 29.
    Shen, Y., Wang, M., Zhang, L., Ma, Y., Ma, B., Zheng, Y., Liu, H., & Luo, J. (2011). Effects of hydroxypropyl-β-cyclodextrin on cell growth, activity, and integrity of steroid-transforming Arthrobacter simplex and Mycobacterium sp. Applied Microbiology and Biotechnology, 90(6), 1995–2003.CrossRefGoogle Scholar
  30. 30.
    Cruz, A., Fernandes, P., Cabral, J., & Pinheiro, H. (2001). Whole-cell bioconversion of β-sitosterol in aqueous–organic two-phase systems. Journal of Molecular Catalysis B: Enzymatic, 11(4-6), 579–585.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.College of Life Sciences, Institute of Microbial EngineeringHenan UniversityKaifengPeople’s Republic of China

Personalised recommendations