Korean Journal of Microbiology (미생물학회지)

The Microbiological Society of Korea (한국미생물학회)
권호 표지

Screening of Edible Mushrooms for the Production of Lovastatin and its HMG-CoA Reductase Inhibitory Activity

Lovastatin을 생산하는 식용버섯 선발과 HMG-CoA reductase 저해 효과

  • Lee Jae-Won (Department of Forest Sciences, College of Agriculture & Life Sciences, Seoul National University) ;
  • Lee Soo-Min (Department of Forest Sciences, College of Agriculture & Life Sciences, Seoul National University) ;
  • Gwak Ki-Seob (Department of Forest Sciences, College of Agriculture & Life Sciences, Seoul National University) ;
  • Lee Ji-Yoon (NICEM, College of Agriculture & Life Sciences, Seoul National University) ;
  • Choi In-Gyu (Department of Forest Sciences, College of Agriculture & Life Sciences, Seoul National University)
  • 이재원 (서울대학교 농업생명과학대학 산림과학부) ;
  • 이수민 (서울대학교 농업생명과학대학 산림과학부) ;
  • 곽기섭 (서울대학교 농업생명과학대학 산림과학부) ;
  • 이지윤 (서울대학교 농업생명과학대학 농업과학공동기기센터) ;
  • 최인규 (서울대학교 농업생명과학대학 산림과학부)
  • Published : 2006.06.01
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Abstract

This research was performed to determine the production of lovastatin and its HMG-CoA reductase activity produced by fruit bodies and mycelial liquid cultures of domestic edible mushrooms (8 fungal strains). By deter-mining TLC analysis for the confirmation of the presence of lovastatin, all the extracts from fruit bodies and mycelial liquid culture showed same Rf value (0.46), whick was identical to that of the standard lovastatin. In order to extract lovastatin from fruit body, the mixture of water/acetonitrile/methanol was chosen as the most effective solvent. Extracts from fruit body and mycelial liquid culture of pleurotus ostreatus produced the high-est lovastatin 0.98 mg/g based on dry biomass, and 21.90 mg/L, respectively. In the inhibition rate of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, the highest was obtained in P. ostreatus as 67.8% among fruit bodies, and the rates of mycelial liquid culture extracts from P. ostreatus and Laetiporus sulphureus were 37.2% and 29.1%, respectively. Unusually L. sulphureus showed high inhibition rate with low content of lovastatin due to the contribution of campesterol and gamma-sitosterol with hypocholesterolemic activity as metabolites.

국내에서 식용버섯으로 이용되고 있는 8종 균주의 자실체와 균사체로부터 콜레스테롤 합성을 저해하는 lovastatin 생산과 고지혈증 억제활성을 탐색하였다. TLC 분석으로 lovastatin생산 유무를 검색한 결과 자실체와 균사체의 추출물에 대해 Rf값이 표준물질콰 같은 약 0.46에서 뚜렷한 밴드가 형성됨을 확인하였다. 자실체로부터 lovastatin 추출을 위한 용매로는 water/acetonitrile/methanol (5:2.5:2.5)을 사용하였을 매 가장 효과적인 lovastatin 생산량을 보였다. Lovastatin 생산량은 자실체 중에서는 Pleurotus ostreatus가 0.98 mg/g (dry biomass)으로 가장 높은 생산량을 나타냈고 균사체 배양액 추출물에 대해서도 P. ostreatus가 21.90 mg/L로 높은 생산량을 나타냈다. 3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase 저해활성에서는 자실체에서 P ostreatus가 67.8%, 균사체에서 P. ostreatus와Laetiporus sulphureus가 각각 37.2%, 29.1%의 저해활성을 보였다. L. sulphureus는 lovastatin 생산량에 비해 높은 저해활성을 나타내서 lovastatin 이외의 다른 고지혈증 억제물질을 GC/MS로 분석한 결과 대사산물로 분비되는 식물성 sterol 물질인 campesterol과 gamma-sitosterol이 검출되었다.

Keywords

References

  1. Bang, I. Y., S. H. Whang, J. W. Kim, S. Y. Kim, and C. S. Park. 2003. Screening of fungal strains producing lovastatin, an antihypercholesterolemin agent. Korean J. Food Sci. Technol. 35, 442-446
  2. Bradford, M. M. 1976. A rapid and sensitive for the quantitation of microgram quantities of protein utilizing the principle of proteindye binding. Anal. Biochem. 72, 248-254 https://doi.org/10.1016/0003-2697(76)90527-3
  3. Connor, W. E., D. S. Lin, A. S. Pappu, J. Frohlich, and G. Gerhard. 2005. Dietary sitostanol and campestanol: accumulation in the blood of humans with sitosterolemia and xanthomatosis and in rat tissues. Lipids. 40, 919-923 https://doi.org/10.1007/s11745-005-1452-7
  4. Erturk, S., A. Onal, and S. M. Cetin. 2003. Analytical methods for the quantitative determination of 3-hydroxy-3methylglutaryl coenzyme A reductase inhibitors in biological samples. J. Chromatogr. B. 793, 193-205 https://doi.org/10.1016/S1570-0232(03)00314-3
  5. Friedrich, J., M. Zuzek, M. Bencina, A. Cimerman, A. Strancar, and I. Radez. 1995. High-performance liquid chromatographic analysis of mevinolin as mevinolinic acid in fermentation broths. J. Chromatogr. A. 704, 363-367 https://doi.org/10.1016/0021-9673(95)00096-6
  6. Gunde-Cimerman, N., and A. Cimerman. 1995. Peurotus fruiting bodies contain the inhibitor of 3-Hydroxy-3-Methylglutaryl- Coenzyme A reductase- Lovastatin. Exp. Mycol. 19, 1-6 https://doi.org/10.1006/emyc.1995.1001
  7. Gunde-Cimerman, N., J. Friedrich, A. Cimerman, and N. Benicki. 1993. Screening fungi for the production of an inhibitor of HMG Co A reductase: Production of mevinolin by the fungi of the genus Pleurotus. FEMS Lett. 111, 203-206 https://doi.org/10.1111/j.1574-6968.1993.tb06386.x
  8. Gunde-Cimerman, N., A. Plemenitas, and A. Cimerman. 1993. Pleurotus fungi produce mevinolin, an inhibitor of HMG Co A reductase. FEMS Lett. 113, 333-338 https://doi.org/10.1111/j.1574-6968.1993.tb06536.x
  9. Gyorgy, S., M. Gyorgy, and P. T. Robert. 1998. Production of lovastatin by a wild strain of Aspergillus terreus. Biotechnol. Lett. 20, 411-415 https://doi.org/10.1023/A:1005391716830
  10. Ha, T.Y., I. J. Cho, and S. H. Lee. 1998. Screening of HMG-CoA reductase inhibitory activity of ethanol and methanol extracts from cereals and regumes. Korean J. Food Sci. Technol. 30, 224-229
  11. Hajjaj, H., P. Niederberger, and P. Duboc. 2001. Lovastatin biosynthesis by Aspergillus terreus in a chemically defined medium. Appl. Envron. Mirobiol. 67, 2596-2602 https://doi.org/10.1128/AEM.67.6.2596-2602.2001
  12. Hulcher, F.H. and W. H. Olesson. 1987. Simplified spectrophotometric assay for microsmal-hydroxy-3-methylglutaryl CoA reductase by measurement of coenzyme. Am. J. Lipid Res. 14, 625-630
  13. Manzoni, M. and M. Rollini. 2002. Biosynthesis and biotechnological production of statins by filamentous fungi and application of these cholesterol-lowering drugs. Appl. Microbiol. Biotechnol. 58, 555-564 https://doi.org/10.1007/s00253-002-0932-9
  14. Moon, Y.J., K. H. Yeom, and C. K. Sung. 2002. Screening of 3- Hydroxy-3-Methylglutaryl-Coenzyme A reductase inhibitors in vitro and its application to pullets. Korean J. Food & Nutr. 15, 307-313
  15. Sudhop, T., Y. Sahin, B. Lindenthal, C. Hahn, C. Luers, H. K. Berthold, and K. Bergmann. 2002. Comparison of the hepatic clearances of campesterol, sitosterol, and cholesterol in healthy subjects suggests that dfflux transporters controlling intestinal sterol absorption also regulate biliary secretion. GUT. 51, 860-863 https://doi.org/10.1136/gut.51.6.860
  16. Szakacs, G., G. Morovjan, and R. P. Tengerdy. 1998. Production of lovastatin by a wild strain of Aspergillus terreus. Biotechnol. Lett. 20, 411-415 https://doi.org/10.1023/A:1005391716830
  17. Tobert, J.A. 1987. New developments in lipid-lowering therapy: the role of inhibitors of hydroxymethyl-glutaryl-coenzyme A reductase. Circulation 76, 534-538 https://doi.org/10.1161/01.CIR.76.3.534
  18. Valera, H.R., J. Gomes, S. Lakshmi, R. Gururaja, S. Suryanarayan, and D. Kumar. 2005. Lovastatin production by solid state fermentation using Aspergillus flavipes. Enzyme Microb. Technol. 37, 521-526 https://doi.org/10.1016/j.enzmictec.2005.03.009