Production of Lovastatin in Solid Culture

고체 배양법에 의한 Lovastatin생산

  • Published : 2004.03.01


Cultivation conditions for overproduction of lovastatins were investigated from the lovastatin producing strain N-03 which was obtained with NTG (N-methyl-N'-nitro-nitrosoguanidine) treatment from Aspergiliu ferrous ATCC 20542. Produced lactone and acid form of lovastatin were detected, and analyzed by HPLC method. In liquid culture, medium No. 2 containing soy protein produced higher amounts of the lovastatins than medium No. 1 (contained rapeseed oil). In solid culture, maximum production was obtained at 28$^{\circ}C$ for 15 days cultivation using cooked wheat bran. For the overproduction of lovastatin from this strain, solid culture method using plastic bag is more superior than liquid culture.


  1. Slater EE, Macdonald JS. 1988. Mechanism of action and biological profile of HMG CoA reductase inhibitors. A new therapeutic alternative. Drugs 36: 72-82.
  2. Finkelstein DB, Ball C. 1992. Biotechnology of filamentous fungi. Butterworth-Heineman, London, UK. p 241-251.
  3. Michael HD, Peter L, Jim XS, Gale P, Edward W, Arnold S, Robert N, Lawrence F. 2002. A multiple-dose pharmacodynamic, safety, and pharmacokinetic comparison of extended and immediate-release formulations of lovastatin. Clinical Therapeutics 24: 112-125.
  4. Hubert S, Renana S, Hedi G, Markus N, Heinrich W, Winfried M. 2001. Effect of atorvastatin, simvastatin, and lovastatin on the metabolism of cholesterol and triacylglycerides in HepG2 cells. Biochemical Pharmacology 62: 1545-1555.
  5. Brown MS, Faust JR, Goldsten JL, Kaneko I, Endo A. 1978. Induction of 3-hydroxy-methylglutaryl-coenzyme, A reductase activity in human firboblasts incubated with compactin (ML-236B), a competitive inhibitor of the reductase. J Biol Chem 253: 1121-1128.
  6. Endo A, Kuroda M, Tarazawa K. 1976. Competitive inhibitor of 3-hydroxy-methylglutaryl-coenzyme A reductase by MC-230A and ML-236 B fungal metabolites having hypocholesterolemic activity. FEBS Lett 72: 323-326.
  7. Alberts AW, Chen J, Kuron G, Hunt V, Huff J, Hoffman C, Rothrock J, Lopez M, Joshua H, Harris E, Patchett A, Monaghan R, Currie S, Stapley E, Alberts-Schonbert G, Hensens O, Hirshfield J, Hoogsteen K, Leish J, Springer J. 1980. Mevinolin: a highly protent competetive inhibitor of hydroxy-methylglutaryl-coenzyme, A reductase and a cholesterol-lowering agent. Proc Natl Acad Sci 77: 3957-3961.
  8. Endo A. 1985. Compactin (ML-236B) and related compound as potential cholesterol-lowering agents that inhibit HMG-CoA reductase. J Med Chem 28: 401-405.
  9. Domsch KH, Gams W. 1980. Compendium of soil fungi. Academic press, London. Vol 1, p 114-117.
  10. Endo A, Negishi Y, Iwashita T, Mizukawa K, Hirama M. 1985. Biosynthesis of ML-236B (compactin) and monacolin K. J Antibiot 38: 444-448.
  11. Tobert JA. 1988. Efficacy andlLong-term adverse effect pattern of lovastatin. J American Cardiology 62: 28-34
  12. Matilde M, Silvia B, Manuela R, Valeria C. 1999. Production of statins by filamentous fungi. Biotechnology 21: 253-257.
  13. Soheil N, Rune B, June M, Erlend BS, Bjorn E, Kaare RN, Heidi KB. 1999. Lovastatin inhibits G1/S transition of normal human B-lymphocytes independent of apoptosis. Experimental Cell Research 252: 144-153.
  14. Srinivasu MK, Narasa RA, Om RG. 2002. Determination of lovastatin and simvastatin in pharmaceutical dosage forms by MEKC. J Pharmaceutical and Biomedical Analysis 29: 715-721
  15. Casas Lopez JL, Sanchez Perez JA, Ferenandez Sevilla JM, Acien Fernandez FG, Molina Grima E, Chisti Y. 2003. Production of lovastatin by Aspergillus terreus : effects of the C:N ratio and the principal nutrients on growth and metabolite production. Enzyme and Microbial Technology 33: 270-277.
  16. Yu TS, Kim J, Kim HS, Hyun JS, Ha HP, Park MG. 1998. Bibliographical study on microorganism of traditional Korea nuruk (since 1945). J Korean Soc Food Sci Nutr 27: 789-799.
  17. Gyorgy Szakacs, Gyorgy Morovjan, Robert PT. 1998. Production of lovastatin by a wild strain of Aspergillus terreus. Biotechnology Lett 20: 411-415.
  18. Kumar MS, Kumar PM, Sarnaik HM, Sadhukhan AK. 2000. A rapid technique for screening of lovastatin-producting strains of Aspergillus terreus by agar plug and Neurospora crassa bioassay. J Microbiological Methods 40: 99-104.