Skip to main content
Log in

Screening of Compactin-Resistant Microorganisms Capable of Converting Compactin to Pravastatin

  • Published:
Current Microbiology Aims and scope Submit manuscript

Abstract

A simple method of using compactin for effective screening of microbial strains with high hydroxylation activity at the 6β position of compactin was developed. Agar plates containing different carbon sources and 500 μg compactin mL−1 were used to screen the microorganisms that can convert compactin to pravastatin. About 100 compactin-resistant strains were isolated from the Basal agar containing 7% (w/v) mannitol as a carbon source, in which two bacteria, Pseudomocardia autotrophica BCRC 12444 and Streptomyces griseolus BCRC 13677, capable of converting compactin to pravastatin with the yield of 20 and 32% (w/w), respectively, were found. High-performance liquid chromatography using C-18 column and two sequential mobile phases, 30% and 50% (v/v) acetonitrile, was also established to simultaneously determine the concentration of compactin and pravastatin in the culture broth. As such, about 2% of target microorganisms could be obtained from the screening program.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Literature Cited

  1. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402

    Article  PubMed  CAS  Google Scholar 

  2. Arai M, Serizawa N, Terahara A, Tsujita Y, Tanaka M, Masuda H, Ishikawa S (1988) Pravastatin sodium (CS-514), a novel cholesterol-lowering agent which inhibits HMG-CoA reductase. Sankyo Kenkyusyo Nenpo 40:1–38

    CAS  Google Scholar 

  3. Bauer S, Mwinyi J, Stoeckle A, Gerloff T, Roots I (2005) Quantification of pravastatin in human plasma and urine after solid phase extraction using high performance liquid chromatography with ultraviolet detection. J Chromatogr B Anal Technol Biomed Life Sci 818:257–262

    CAS  Google Scholar 

  4. Endo A, Kuroda M, Tsujita Y (1976) ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis produced by Penicillium citrinium. J Antibiot (Tokyo) 29:1346–1348

    CAS  Google Scholar 

  5. 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. Biotechnol Bioeng 42:815–820

    Article  CAS  Google Scholar 

  6. Matsuoka T, Miyakoshi S, Tanzawa K, Nakahara K, Hosobuchi M, Serizawa N (1989) Purification and characterization of cytochrome P-450sca from Streptomyces carbophilus. ML-236B (compactin) induces a cytochrome P-450sca in Streptomyces carbophilus that hydroxylates ML-236B to pravastatin sodium (CS-514), a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase. Eur J Biochem 184:707–713

    Article  PubMed  CAS  Google Scholar 

  7. Park JW, Lee JK, Kwon TJ, Yi DH, Kim YJ, Moon SH, Suh HH, Kang SM, Park YI (2003) Bioconversion of compactin into pravastatin by Streptomyces sp. Biotechnol Lett 25:1827–1831

    Article  PubMed  CAS  Google Scholar 

  8. Peng Y, Yashphe J, Demain AL (1997) Biotransformation of compactin to pravastatin by Actinomadura sp. 2966. J Antibiot (Tokyo) 50:1032–1035

    CAS  Google Scholar 

  9. Serizawa N, Nakagawa K, Tsujita Y, Terahara A, Kuwano H (1983) 3 alpha-Hydroxy-ML-236B (3 alpha-hydroxycompactin), microbial transformation product of ML-236B (compactin). J Antibiot (Tokyo) 36:608–610

    CAS  Google Scholar 

  10. Serizawa N, Nakagawa K, Tsujita Y, Terahara A, Kuwano H, Tanaka M (1983) 6 alpha-Hydroxy-iso-ML-236B (6 alpha-hydroxy-iso-compactin) and ML-236A, microbial transformation products of ML-236B. J Antibiot (Tokyo) 36:918–920

    CAS  Google Scholar 

  11. Serizawa N, Serizawa S, Nakagawa K, Furuya K, Okazaki T, Terahara A (1983) Microbial hydroxylation of ML-236B (compactin), studies on microorganisms capable of 3,â-hydroxylation of ML-236B. J Antibiot (Tokyo) 36:887–891

    CAS  Google Scholar 

  12. Serizawa N, Matsuoka T (1991) A two component-type cytochrome P-450 monooxygenase system in a prokaryote that catalyzes hydroxylation of ML-236B to pravastatin, a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Biochim Biophys Acta 1084:35–40

    PubMed  CAS  Google Scholar 

  13. Serizawa N (2000) Biocatalytic production of pravastatin, an anticholesterol drug. In: Patel RN (ed) Stereoselective biocatalysis. New York: Marcel Dekker, pp 703–711

    Google Scholar 

  14. Tsujita Y, Kuroda M, Shimada Y, Tanzawa K, Arai M, Kaneko I, Tanaka M, Masuda H, Tarumi C, Watanabe Y, et al. (1986) CS-514, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase: tissue-selective inhibition of sterol synthesis and hypolipidemic effect on various animal species. Biochim Biophys Acta 877:50–60

    PubMed  CAS  Google Scholar 

  15. Weisburg WG, Barns SM, Pelletier DA, Lane DJ (1991) 16S ribosomal DNA amplification for phylogenetic study. J Bacteriol 173:697–703

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants NSC 92-2311-B-005-016 from the National Science Council of the Republic of China and CMU93-MT-06 from the China Medical University.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hui-Yu Hu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, CH., Hu, HY., Cho, YC. et al. Screening of Compactin-Resistant Microorganisms Capable of Converting Compactin to Pravastatin. Curr Microbiol 53, 108–112 (2006). https://doi.org/10.1007/s00284-005-0276-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00284-005-0276-7

Keywords

Navigation