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Biotransformation of Steroids and Flavonoids by Cultures of Aspergillus niger

Abstract

Steroids are derivatives of the triterpenoid squalene, containing three fused cyclohexane rings and a cyclopentane ring, and flavonoids are derivatives of L-phenylalanine, containing two aromatic rings joined by a three-carbon bridge that may form part of a heterocyclic ring. A great variety of steroids and flavonoids are produced by plants, and many additional steroids are produced by animals or fungi. Because these compounds have many nutritional and pharmaceutical values, and many of them cannot be produced by chemical synthesis, biotechnological processes are being developed that use cultures of Aspergillus niger and other fungi to transform steroids and flavonoids to a variety of metabolites. These biochemical reactions, including hydroxylation, dehydrogenation, O-methylation, demethylation, cleavage of rings, epoxide hydrolysis, double bond reduction, and others, may be used for the production of higher-value compounds.

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References

  1. Fernandes, P., & Cabral, J. M. S. (2007). Phytosterols: applications and recovery methods. Bioresource Technology, 98, 2335–2350.

    CAS  Article  Google Scholar 

  2. Kumar, S., Pandey, A. K. (2013). Chemistry and biological activities of flavonoids: an overview. Scientific World Journal, 162750 (16 p.)

  3. Liu, J.-H., & Yu, B.-Y. (2010). Biotransformation of bioactive natural products for pharmaceutical lead compounds. Current Organic Chemistry, 14, 1400–1406.

    CAS  Article  Google Scholar 

  4. Pervaiz, I., Ahmad, S., Madni, M. A., Ahmad, H., & Khaliq, F. H. (2013). Microbial biotransformation: a tool for drug designing. Applied Biochemistry and Microbiology, 49, 437–450.

    CAS  Article  Google Scholar 

  5. Das, S., & Rosazza, J. P. N. (2006). Microbial and enzymatic transformations of flavonoids. Journal of Natural Products, 69, 499–508.

    CAS  Article  Google Scholar 

  6. Tournas, V. H., Kohn, J. S., & Katsoudas, E. J. (2011). Interactions between various microbes and ginseng botanicals. Critical Reviews in Microbiology, 37, 113–120.

    CAS  Article  Google Scholar 

  7. Donova, M. V., & Egorova, O. V. (2012). Microbial steroid transformations: current state and prospects. Applied Microbiology and Biotechnology, 94, 1423–1447.

    CAS  Article  Google Scholar 

  8. Meyer, V., Wu, B., & Ram, A. F. J. (2011). Aspergillus as a multi-purpose cell factory: current status and perspectives. Biotechnology Letters, 33, 469–476.

    CAS  Article  Google Scholar 

  9. Zheng, X. X., Chen, R. S., Shen, Y., & Yin, Z. Y. (2014). Phytosterols elevation in bamboo shoot residue through laboratorial scale solid-state fermentation using isolated Aspergillus niger CTBU. Applied Biochemistry and Biotechnology, 172, 4078–4083.

    CAS  Article  Google Scholar 

  10. Parshikov, I. A., & Sutherland, J. B. (2014). The use of Aspergillus niger cultures for biotransformation of terpenoids. Process Biochemistry, 49, 2086–2100.

    CAS  Article  Google Scholar 

  11. Schuster, E., Dunn-Coleman, N., Frisvad, J. C., & Van Dijck, P. W. M. (2002). On the safety of Aspergillus niger—a review. Applied Microbiology and Biotechnology, 59, 426–435.

    CAS  Article  Google Scholar 

  12. Vaija, J., Linko, Y.-Y., & Linko, P. (1982). Citric acid production with alginate bead entrapped Aspergillus niger ATCC 9142. Applied Biochemistry and Biotechnology, 7, 51–54.

    CAS  Article  Google Scholar 

  13. Ramachandran, S., Fontanille, P., Pandey, A., & Larroche, C. (2006). Gluconic acid: properties, applications and microbial production. Food Technology and Biotechnology, 44, 185–195.

    CAS  Google Scholar 

  14. Bram, B., & Solomons, G. L. (1965). Production of the enzyme naringinase by Aspergillus niger. Applied Microbiology, 13, 842–845.

    CAS  Google Scholar 

  15. Wang, C. L., Wu, G. H., Chen, C., & Chen, S. L. (2012). High production of β-glucosidase by Aspergillus niger on corncob. Applied Biochemistry and Biotechnology, 168, 58–67.

    CAS  Article  Google Scholar 

  16. Bansal, N., Janveja, C., Tewari, R., Soni, R., & Soni, S. K. (2014). Highly thermostable and pH-stable cellulases from Aspergillus niger NS-2: properties and application for cellulose hydrolysis. Applied Biochemistry and Biotechnology, 172, 141–156.

    CAS  Article  Google Scholar 

  17. Holland, H. L., & Auret, B. J. (1975). The mechanism of the microbial hydroxylation of steroids. Part 1. The C-21 hydroxylation of progesterone by Aspergillus niger ATCC 9142. Canadian Journal of Chemistry, 53, 845–854.

    CAS  Article  Google Scholar 

  18. Yamashita, H., Shibata, K., Yamakoshi, N., Kurosawa, Y., & Mori, H. (1976). Microbial 16β-hydroxylation of steroids with Aspergillus niger. Agricultural and Biological Chemistry, 40, 505–509.

    CAS  Article  Google Scholar 

  19. Peart, P. C., Reynolds, W. F., & Reese, P. B. (2013). The facile bioconversion of testosterone by alginate-immobilised filamentous fungi. Journal of Molecular Catalysis B: Enzymatic, 95, 70–81.

    CAS  Article  Google Scholar 

  20. Auret, B. J., & Holland, H. L. (1971). Microbiological 18-hydroxylation of steroids. Journal of the Chemical Society D: Chemical Communications, 1971, 1157.

    Article  Google Scholar 

  21. Peart, P. C., Chen, A. R. M., Reynolds, W. F., & Reese, P. B. (2012). Entrapment of mycelial fragments in calcium alginate: a general technique for the use of immobilized filamentous fungi in biocatalysis. Steroids, 77, 85–90.

    CAS  Article  Google Scholar 

  22. Hu, S.-H., Tian, X.-F., Sun, Y.-H., & Han, G.-D. (1996). Microbial hydroxylation of 13-ethyl-17β-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one. Steroids, 61, 407–410.

    CAS  Article  Google Scholar 

  23. Atta-ur-Rahman, Choudhary, M. I., Shaheen, F., Ashraf, M., & Jahan, S. (1998). Microbial transformations of hypolipemic E-guggulsterone. Journal of Natural Products, 61, 428–431.

    CAS  Article  Google Scholar 

  24. Choudhary, M. I., Azizuddin, & Atta-ur-Rahman. (2002). Microbial transformation of danazol. Natural Product Letters, 16, 101–106.

  25. Al-Aboudi, A., Mohammad, M. Y., Haddad, S., Al-Far, R., Choudhary, M. I., & Atta-ur-Rahman. (2009). Biotransformation of methyl cholate by Aspergillus niger. Steroids, 74, 483–486.

    CAS  Article  Google Scholar 

  26. Khan, N. T., Bibi, M., Yousuf, S., Qureshi, I. H., Atta-ur-Rahman, Al-Majid, A. M., Mesaik, M. A., Khalid, A. S., Sattar, S. A., Atia-tul-Wahab, & Choudhary, M. I. (2012). Synthesis of some potent immunomodulatory and anti-inflammatory metabolites by fungal transformation of anabolic steroid oxymetholone. Chemistry Central Journal, 6, 153.

  27. Zafar, S., Bibi, M., Yousuf, S., & Choudhary, M. I. (2013). New metabolites from fungal biotransformation of an oral contraceptive agent: methyloestrenolone. Steroids, 78, 418–425.

    CAS  Article  Google Scholar 

  28. Chen, G., Yang, X., Li, J., Ge, H., Song, Y., & Ren, J. (2013). Biotransformation of 20(S)-protopanaxadiol by Aspergillus niger AS 3.1858. Fitoterapia, 91, 256–260.

    CAS  Article  Google Scholar 

  29. Riguera, R. (1997). Isolating bioactive compounds from marine organisms. Journal of Marine Biotechnology, 5, 187–193.

    CAS  Google Scholar 

  30. Hostettmann, K., & Marston, A. (2005). Saponins. Cambridge: Cambridge University Press.

    Book  Google Scholar 

  31. Chi, H., & Ji, G.-E. (2005). Transformation of ginsenosides Rb1 and Re from Panax ginseng by food microorganisms. Biotechnology Letters, 27, 765–771.

    CAS  Article  Google Scholar 

  32. Chi, H., Kim, D.-H., & Ji, G.-E. (2005). Transformation of ginsenosides Rb2 and Rc from Panax ginseng by food microorganisms. Biological and Pharmaceutical Bulletin, 28, 2102–2105.

    CAS  Article  Google Scholar 

  33. Liu, L., Gu, L.-J., Zhang, D.-L., Wang, Z., Wang, C.-Y., Li, Z., & Sung, C.-K. (2010). Microbial conversion of rare ginsenoside Rf to 20(S)-protopanaxatriol by Aspergillus niger. Bioscience Biotechnology Biochemistry, 74, 96–100.

    CAS  Article  Google Scholar 

  34. He, X., Liu, B., Wang, G., Wang, X., Su, L., Qu, G., & Yao, X. (2006). Microbial metabolism of methyl protodioscin by Aspergillus niger culture—a new androstenedione producing way from steroid. Journal of Steroid Biochemistry and Molecular Biology, 100, 87–94.

    CAS  Article  Google Scholar 

  35. Yum, C. H., You, H. J., & Ji, G. E. (2010). Cytotoxicity of dioscin and biotransformed fenugreek. Journal of the Korean Society of Applied Biology and Chemistry, 53, 470–477.

    CAS  Article  Google Scholar 

  36. Zhou, W.-B., Feng, B., Huang, H.-Z., Liu, P., Yu, H.-S., Zhao, Y., Qin, Y.-J., Kang, L.-P., & Ma, B.-P. (2010). Hydrolysis of timosaponin BII by the crude enzyme from Aspergillus niger AS 3.0739. Journal of Asian Natural Products Research, 12, 955–961.

    CAS  Article  Google Scholar 

  37. Kadis, B. (1978). Steroid epoxides in biologic systems: a review. Journal of Steroid Biochemistry, 9, 75–81.

    CAS  Article  Google Scholar 

  38. Choi, W. J. (2009). Biotechnological production of enantiopure epoxides by enzymatic kinetic resolution. Applied Microbiology and Biotechnology, 84, 239–247.

    CAS  Article  Google Scholar 

  39. He, X., Tang, J., Qiao, A., Wang, G., Jiang, M., Liu, R. H., & Yao, X. (2006). Cytotoxic biotransformed products from cinobufagin by Mucor spinosus and Aspergillus niger. Steroids, 71, 392–402.

    CAS  Article  Google Scholar 

  40. Bisogno, F. R., Orden, A. A., Pranzoni, C. A., Cifuente, D. A., Giordano, O. S., & Sanz, M. K. (2007). Atypical regioselective biohydrolysis on steroidal oxiranes by Aspergillus niger whole cells: some stereochemical features. Steroids, 72, 643–652.

    CAS  Article  Google Scholar 

  41. Lu, J., Deng, S., Chen, H., Hou, J., Zhang, B., Tian, Y., Wang, C., & Ma, X. (2013). Microbial transformation of cinobufotalin by Alternaria alternata AS 3.4578 and Aspergillus niger AS 3.739. Journal of Molecular Catalysis B: Enzymatic, 89, 102–107.

    CAS  Article  Google Scholar 

  42. Lin, C.-Y., Huo, C., Kuo, L.-K., Hiipakka, R. A., Jones, R. B., Lin, H.-P., Hung, Y., Su, L.-C., Tseng, J.-C., Kuo, Y.-Y., Wang, Y.-L., Fukui, Y., Kao, Y.-H., Kokontis, J. M., Yeh, C.-C., Chen, L., Yang, S.-D., Fu, H.-H., Chen, Y.-W., Tsei, K. K. C., Chang, J.-Y., & Chuu, C.-P. (2013). Cholestane-3β,5α,6β-triol suppresses proliferation, migration, and invasion of human prostate cancer cells. PloS One, 8, e65734.

  43. Havsteen, B. H. (2002). The biochemistry and medical significance of the flavonoids. Pharmacology & Therapeutics, 96, 67–202.

    CAS  Article  Google Scholar 

  44. Alarcón, J., Alderete, J., Escobar, C., Araya, R., & Cespedes, C. L. (2013). Aspergillus niger catalyzes the synthesis of flavonoids from chalcones. Biocatalysis and Biotransformation, 31, 160–167.

    Article  Google Scholar 

  45. Ibrahim, A. R., & Abul-Hajj, Y. J. (1990). Microbial transformation of flavone and isoflavone. Xenobiotica, 20, 363–373.

    CAS  Article  Google Scholar 

  46. Mahmoud, Y. A., Assawah, S. W., El-Sharkawy, S. H., & Abdel-Salam, A. (2008). Flavone biotransformation by Aspergillus niger and the characterization of two newly formed metabolites. Mycobiology, 36, 121–133.

    CAS  Article  Google Scholar 

  47. Ibrahim, A.-R., & Abul-Hajj, Y. J. (1990). Microbiological transformation of (±)-flavanone and (±)-isoflavanone. Journal of Natural Products, 53, 644–656.

    CAS  Article  Google Scholar 

  48. Kostrzewa-Suslow, E., Dmochowska-Gladysz, J., Bialonska, A., Ciunik, Z., & Rymowicz, W. (2006). Microbial transformations of flavanone and 6-hydroxyflavanone by Aspergillus niger strains. Journal of Molecular Catalysis B: Enzymatic, 39, 18–23.

    CAS  Article  Google Scholar 

  49. Kostrzewa-Suslow, E., Dmochowska-Gladysz, J., Bialońska, A., & Ciunik, Z. (2008). Microbial transformations of flavanone by Aspergillus niger and Penicillium chermesinum cultures. Journal of Molecular Catalysis B: Enzymatic, 52–53, 34–39.

    Article  Google Scholar 

  50. Kostrzewa-Suslow, E., & Janeczko, T. (2012). Microbial transformations of 7-hydroxyflavanone. Scientific World Journal, 254929. (8 p.)

  51. Westlake, D. W. S., Talbot, G., Blakley, E. R., & Simpson, F. J. (1959). Microbial decomposition of rutin. Canadian Journal of Microbiology, 5, 621–629.

    CAS  Article  Google Scholar 

  52. You, H. J., Ahn, H. J., & Ji, G. E. (2010). Transformation of rutin to antiproliferative quercetin-3-glucoside by Aspergillus niger. Journal of Agricultural and Food Chemistry, 58, 10886–10892.

    CAS  Article  Google Scholar 

  53. Haluk, J. P., & Metche, M. (1970). Transformation microbiologique de la quercétine par Aspergillus niger van Tieghem. Bulletin de la Société de Chimie Biologique, 52, 667–677.

    CAS  Google Scholar 

  54. Xu, J., Yang, L., Zhao, S.-J., Wang, Z.-T., & Hu, Z.-B. (2012). An efficient way from naringenin to carthamidine and isocarthamidine by Aspergillus niger. World Journal of Microbiology and Biotechnology, 28, 1803–1806.

    CAS  Article  Google Scholar 

  55. Sakai, S. (1977). Degradation of the plant flavonoid phellamurin by Aspergillus niger. Applied and Environmental Microbiology, 34, 500–505.

    CAS  Google Scholar 

  56. Okuno, Y., & Miyazawa, M. (2004). Biotransformation of nobiletin by Aspergillus niger and the antimutagenic activity of a metabolite, 4’-hydroxy-5,6,7,8,3’-pentamethoxyflavone. Journal of Natural Products, 67, 1876–1878.

    CAS  Article  Google Scholar 

  57. Buisson, D., Quintin, J., & Lewin, G. (2007). Biotransformation of polymethoxylated flavonoids: access to their 4’-O-demethylated metabolites. Journal of Natural Products, 70, 1035–1038.

    CAS  Article  Google Scholar 

  58. Mohamed, A. E. H. H., Khalafallah, A. K., & Yousof, A. H. (2008). Biotransformation of glabratephrin, a rare type of isoprenylated flavonoids, by Aspergillus niger. Zeitschrift für Naturforschung, 63c, 561–564.

  59. Kostrzewa-Suslow, E., Dmochowska-Gladysz, J., Janeczko, T., Sroda, K., Michalak, K., & Palko, A. (2012). Microbial transformations of 6- and 7-methoxyflavones in Aspergillus niger and Penicillium chermesinum cultures. Zeitschrift für Naturforschung, 67c, 411–417.

    Article  Google Scholar 

  60. Kostrzewa-Suslow, E., Dymarska, M., & Janeczko, T. (2014). Microbial transformations of 3-methoxyflavone by strains of Aspergillus niger. Polish Journal of Microbiology, 63, 111–114.

    CAS  Google Scholar 

  61. Kostrzewa-Suslow, E., & Janeczko, T. (2014). Microbial transformations of 5-hydroxy- and 5-methoxyflavone in Aspergillus niger and Penicillium chermesinum cultures. Journal of Microbiology Biotechnology and Food Sciences, 3, 448–452.

    CAS  Google Scholar 

  62. Kostrzewa-Suslow, E., & Janeczko, T. (2012). Microbial transformations of 7-methoxyflavanone. Molecules, 17, 14810–14820.

    CAS  Article  Google Scholar 

  63. Kostrzewa-Suslow, E., Dymarska, M., Bialońska, A., & Janeczko, T. (2014). Enantioselective conversion of certain derivatives of 6-hydroxyflavanone. Journal of Molecular Catalysis B: Enzymatic, 102, 59–65.

    CAS  Article  Google Scholar 

  64. Gardana, C., Canzi, E., & Simonetti, P. (2009). The role of diet in the metabolism of daidzein by human faecal microbiota sampled from Italian volunteers. Journal of Nutritional Biochemistry, 20, 940–947.

    CAS  Article  Google Scholar 

  65. Rafii, F., Sutherland, J. B., Bridges, B. M., Park, M., & Adams, M. R. (2012). Relationship of dietary soy protein to daidzein metabolism by cultures of intestinal microfloras from monkeys. Food and Nutrition Sciences, 3, 267–273.

    CAS  Article  Google Scholar 

  66. Mimura, A., Yazaki, S.-I., Tanimura, H. (1998). A potent antioxidative and anti-UV-B isoflavonoids transformed microbiologically from soybean components. In: Functional foods for disease prevention. I. Fruits, vegetables, and teas. (ed. Shibamoto, T., Terao, J., Osawa, T.) American Chemical Society Symposium Series, 701, 127–137.

  67. Miyazawa, M., Ando, H., Okuno, Y., & Araki, H. (2004). Biotransformation of isoflavones by Aspergillus niger, as biocatalyst. Journal of Molecular Catalysis B: Enzymatic, 27, 91–95.

    CAS  Article  Google Scholar 

  68. Miyazawa, M., Takahashi, K., & Araki, H. (2006). Biotransformation of isoflavones by Aspergillus niger as biocatalyst. Journal of Chemical Technology and Biotechnology, 81, 674–678.

    CAS  Article  Google Scholar 

  69. Zhong, K., Zhao, S.-Y., Jönsson, L. J., & Hong, F. (2008). Enzymatic conversion of epigallocatechin gallate to epigallocatechin with an inducible hydrolase from Aspergillus niger. Biocatalysis and Biotransformation, 26, 306–312.

    CAS  Article  Google Scholar 

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Acknowledgments

We thank Dr. C. E. Cerniglia, Dr. S. L. Foley, and Dr. K. A. Woodling for their helpful comments. The views presented in this article do not necessarily reflect those of the U. S. Food and Drug Administration.

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Correspondence to John B. Sutherland.

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Parshikov, I.A., Sutherland, J.B. Biotransformation of Steroids and Flavonoids by Cultures of Aspergillus niger . Appl Biochem Biotechnol 176, 903–923 (2015). https://doi.org/10.1007/s12010-015-1619-x

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Keywords

  • Aspergillus niger
  • Biotransformation
  • Flavonoids
  • Organic compounds
  • Steroids