Skip to main content

In situ bioconversion of compactin to pravastatin by Actinomadura species in fermentation broth of Penicillium citrinum


The biocatalytic production of pravastatin from compactin by hydroxylation has found many applications in health care and pharmaceuticals. Actinomadura macra, Actinomadura madurae, and Actinomadura livida can efficiently bioconvert compactin to pravastatin. The fermentation broth (Penicillium citrinum fermented media) harvested on the eighth day contained 388.90 mg L−1 of compactin and an undetectable level of mycotoxin (citrinin). Bioconversion by A. macra was highest (87 %) in the yeast extract-amended medium. The anti-actinomadura effects of citrinin reduce the bioconversion capacity of Actinomadura. The in situ hydroxylation of compactin produced by P. citrinum represents a preferable alternative for the use of purified compactin, as a way to reduce cost and time processing.

This is a preview of subscription content, access via your institution.


  1. Ahmad, A., Mujeeb, M., & Panda, B. P. (2010). An HPTLC method for the simultaneous analysis of compactin and citrinin in Penicillium citrinum fermentation broth. Journal of Planar Chromatography — Modern TLC, 23, 282–285. DOI: 10.1556/jpc.23.2010.4.8.

    Article  CAS  Google Scholar 

  2. Ahmad, A., Mujeeb, M., & Panda, B. P. (2011a). Production and optimization of mevastatin by Penicillium citrinum MTCC 1256 and effect of citrinin on growth of Actinomadura strains. Latin American Journal of Pharmacy, 30, 496–501.

    CAS  Google Scholar 

  3. Ahmad, A., Panda, B. P., & Mujeeb, M. (2011b). A validated stability-indicating method for simultaneous analysis of mevastatin and pravastatin in fermentation broth during bioconversion by Actinomadura macra. Acta Chromatographica, 23, 121–131. DOI: 10.1556/achrom.23.2011.1.8.

    Article  CAS  Google Scholar 

  4. Barrios-González, J., & Miranda, R. U. (2010). Biotechnological production and applications of statins. Applied Microbiology and Biotechnology, 85, 869–883. DOI: 10.1007/s00253-009-2239-6.

    Article  Google Scholar 

  5. Chakravarti, R., & Sahai, V. (2002a). A chemically defined medium for production of compactin by Penicillium citrinum. Biotechnology Letters, 24, 527–530. DOI: 10.1023/a:1014895532142.

    Article  CAS  Google Scholar 

  6. Chakravarti, R., & Sahai, V. (2002b). Optimization of compactin production in chemically defined production medium by Penicillium citrinum using statistical methods. Process Biochemistry, 38, 481–486. DOI: 10.1016/s0032-9592(02)00 138-3.

    Article  CAS  Google Scholar 

  7. Chan, W. H. (2008). Effects of citrinin on maturation of mouse oocytes, fertilization, and fetal development in vitro and in vivo. Toxicology Letters, 180, 28–32. DOI: 10.1016/j.toxlet.2008.05.011.

    Article  CAS  Google Scholar 

  8. Chen, C. H., Hu, H. Y., Cho, Y. C., & Hsu, W. H. (2006). Screening of compactin-resistant microorganisms capable of converting compactin to pravastatin. Current Microbiology, 53, 108–112. DOI: 10.1007/s00284-005-0276-7.

    Article  CAS  Google Scholar 

  9. Hosobuchi, M., Kurosawa, K., & Yoshikawa, H. (1993). Application of computer to monitoring and control of fermentation process: Microbial conversion of ML-236B Na to pravastatin. Biotechnology and Bioengineering, 42, 815–820. DOI: 10.1002/bit.260420705.

    Article  CAS  Google Scholar 

  10. Jackson, L. K., & Ciegler, A. (1978). Production and analysis of citrinin in corn. Applied and Environmental Microbiology, 36, 408–411.

    CAS  Google Scholar 

  11. Lin, C. L., Tang, Y. L., & Lin, S. M. (2011). Efficient bioconversion of compactin to pravastatin by the quinolinedegrading microorganism Pseudonocardia carboxydivorans isolated from petroleum-contaminated soil. Bioresource Technology, 102, 10187–10193. DOI: 10.1016/j.biortech.2011.09.029.

    Article  CAS  Google Scholar 

  12. Park, J. W., Lee, J. K., Kwon, T. J., Yi, D. H., Kim, Y. J., Moon, S. H., Suh, H. H., Kang, S. M., & Park, Y. I. (2003). Bioconversion of compactin into pravastatin by Streptomyces sp. Biotechnology Letters, 25, 1827–1831. DOI: 10.1023/a:1026281914301.

    Article  CAS  Google Scholar 

  13. Peng, Y. L., & Demain, A. L. (1998). A new hydroxylase system in Actinomadura sp cells converting compactin to pravastatin. Journal of Industrial Microbiology & Biotechnology, 20, 373–375. DOI: 10.1038/sj.jim.2900539.

    Article  CAS  Google Scholar 

  14. Peng, Y. L., & Demain, A. L. (2000). Bioconversion of compactin to pravastatin by Actinomadura sp. ATCC 55678. Journal of Molecular Catalysis B: Enzymatic, 10, 151–156. DOI: 10.1016/s1381-1177(00)00123-5.

    Article  CAS  Google Scholar 

  15. Shepherd, J., Cobbe, S. M., Ford, I., Isles, C. G., Lorimer, A. R., Macferlane, P. W., McKillop, J. H., & Packard, C. J. (1995). Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. New England Journal of Medicine, 333, 1301–1309. DOI: 10.1056/nejm199511163332001.

    Article  CAS  Google Scholar 

  16. Watanabe, I., Nara, F., & Serizawa, N. (1995). Cloning, characterization and expression of the gene encoding cytochrome P-450sca-in2 from Streptomyces carbophilus involved in production of pravastatin, a specific HMG-CoA reductase inhibitor. Gene, 163, 81–85. DOI: 10.1016/0378-1119(95)00394-l.

    Article  CAS  Google Scholar 

  17. Yamashita, H., Tsubokawa, S., & Endo, A., (1985). Microbial hydroxylation of compactin (ML-236B) and monacolin K. Journal of Antibiotics, 38, 605–609.

    Article  CAS  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Bibhu Prasad Panda.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ahmad, A., Mujeeb, M., Kapoor, R. et al. In situ bioconversion of compactin to pravastatin by Actinomadura species in fermentation broth of Penicillium citrinum . Chem. Pap. 67, 667–671 (2013).

Download citation


  • Actinomadura sp.
  • P. citrinum
  • compactin
  • pravasatin
  • in situ bioconversion