Screening of Fungal Strains Producing Lovastatin, an Antihypercholesterolemic Agent

콜레스테롤합성저해제 lovastatin을 생산하는 곰팡이 균주의 탐색

  • 방인영 (경희대학교 생명과학부 식품공학과) ;
  • 황승환 (인천대학교 생물학과) ;
  • 김정완 (인천대학교 생물학과) ;
  • 김상용 ((주)바이오엔진) ;
  • 박천석 (경희대학교 생명과학부 식품공학과)
  • Published : 2003.06.01

Abstract

Over two hundred fungal strains from Korean soil were tested for the production of cholesterol-lowering agent, lovastatin. Each fungal strain was cultivated in the rapeseedmeal production medium (RPM). After growing for 7 days, the presence of lovastatin in the culture was examined by TLC analysis and HPLC. Nine different fungal strains were determined to produce detectable amounts of lovastatin, among which one fungal strain isolated from barnyard manure of Kanghwa island produced 25.58 mg/L of lovastatin in the production medium. The morphological observation combined with the determination of 18S-rRNA sequence suggested that the selected strain belongs to a member of Aspergillus sp..

인천광역시의 일대와 강화도, 백령도, 제주도 등 한국 토양으로부터 순수분리된 200여 종의 곰팡이 균주에서 콜레스테롤 합성 저해제인 lovastatin의 생산 여부를 확인하였다. Lovastatin 생산은 rapeseed meal이 함유된 RPM 배지를 사용하였고 TLC와 HPLC를 사용하여 lovastatin의 생산을 조사하였다. 결과 200여 균주 중 9개의 균주만이 lovastatind을 생산하였고, HPLC로 확인한 결과 삼성리 퇴비 균주(ISR)에서 25.52 mg/L의 생산량을 보였다. 포자의 형태학적 구조와 18SrRNA 유전자의 염기서열 결과 삼성리 퇴비 균주는 Aspergillus sp.로 확인되었다.

Keywords

References

  1. National Statistical Office. Annual Report on the Cause of Death Statistics. National Statistical Office, Korea (1996)
  2. Sehnal, F. Hormonal role of ecdysteroids in insert larvea and during metamorphosis, pp. 271-278. In: Ecdysone: From Chemistry to Mode of Action. Koolman, J. (ed.). Thieme Medical Publishers, New York, USA (1989)
  3. Grover, S.A., Coupal, L. and Hu, X.P. Identifying adults at increased risk of coronary disease. J. Am. Med. Assoc. 274: 801-806 (1995) https://doi.org/10.1001/jama.274.10.801
  4. Stryer, L. Biochemistry, 4th ed. pp. 685-712. W.H. Freeman & Company, New York, USA (1995)
  5. Tobert, J.A. New developments in lipid-lowering therapy: the role of inhibitors of hydroxymethyl-glutaryl-coenzyme A reductase Circulation 76: 534-538 (1987) https://doi.org/10.1161/01.CIR.76.3.534
  6. Endo, A., Kuroda, M. and Tsujita, Y. ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis produced by Penicillium citrinum. J. Antibiot. 29: 1346-1348 (1976) https://doi.org/10.7164/antibiotics.29.1346
  7. Endo, A., Kuroda, M. and Tanzawa, K. Competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by ML-236A and ML-236B, fungal metabolites, having hypercholesterolemic activity. FEBS Lett. 72: 323-326 (1976) https://doi.org/10.1016/0014-5793(76)80996-9
  8. Alberts, A.W., Chen, J., Kuron, G., Hunt, V., Huff, J., Hoffman, C., Rothrock, J., Lopez, M., Joshua, H.M., Harris, E., Patchett, A., Monaghan, R., Currie, S., Stapley, E., Alberts-Schonberg, G., Hensens, O., Hirshfield, J., Hoogsteen, K., Liesch, J. and Springer, J. Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl coenzyme A reductase and a cholesterollowering agent. Proc. Natl. Acad. Sci. U.S.A. 77: 3957-3961(1980) https://doi.org/10.1073/pnas.77.7.3957
  9. Nina, G.C., Jozica, F., Alesksa, C. and Neda, B. Screening fungi for the production of an inhibitor of HMG CoA reductase: Production of mevinolin by the fungi of the genus Pleurotus. FEMS Microbiol. Lett. 111: 203-206 (1993) https://doi.org/10.1111/j.1574-6968.1993.tb06386.x
  10. Gyorgy, S., Gyorgy, M. and Robert, P.T. Production of lovastatin by a wild strain of Aspergillus terreus. Biotechnol. Lett. 20: 411-415 (1998) https://doi.org/10.1023/A:1005391716830
  11. Sutton, D.A., Fothergill, A.W and Rinaldi, M.G. Guide to Clinically Significant Fungi. Williams & Wilkins, Baltimore, USA (1998)
  12. Sitaram Kumar, M., Pallapothu, M.K., Hemant M.S and Sadhukhan, A.K. A rapid technique for screening of lovastatinproducing strains of Aspergillus terreus by agar plug and Neurospora crassa bioassay. J. Microbiol. Methods 40: 99-104 (2000) https://doi.org/10.1016/S0167-7012(99)00135-9
  13. Murray, P.R., Baron, E.J., Pfaller, M.A, Tenover, F.C and Yolken, R.H. Manual of Clinical Microbiology. pp. 699-854. American Society for Microbiology, Washington, DC, USA (1995)
  14. St-Germain, G. and Summerbell, R. Identifying Filamentous Fungi. Star Publishing Company, Belmont (1996)