Abstract
The biosynthesis of Lovastatin, a cholesterol lowering agent formed by the filamentous fungus Aspergillus terreus, was investigated in shaking flask. The effects of essential elements in the experimental medium such as carbon, nitrogen, phosphate sources, and amino acids were examined to increase Lovastatin productivity. Lovastatin production in shaking flasks was 68 mg/L in the used medium. Effect of carbon source on Lovastatin production was performed. As a carbon source in the medium, 45 mL/L of glycerol increased the Lovastatin production up to 256 mg/L, which was found to be improved almost 3.5 times in comparison with that in common medium. The optimum concventration of peptonized milk as nitrogen source was obtained 30g/L on Lovastatin production. The severe inhibition of the cell growth and the Lovastatin production were observed in shaking flasks conducted at the medium contained ammonium carbonate as a nitrogen source. Lovastatin production various concentrations of several phosphate compounds was also examined. The addition of either potassium phosphate diabsic or sodium phosphate dibasic increased the Lovastatin production and the optimal level of potassium phosphate dibasic was 6 g/L. Even though Lovastatin contain methionine-derived methyl group, L-methionine and DL-methionine tend to diminish the Lovastatin production. Among the amino acids, L-histidine and L-tryptophan had a remarkable enhancing effect on the Lovastatin production. The optimal concentration of L-histidine and L-tryptophan was 6g/L.
고지혈증 치료제인 Lovastatin을 Aspergillus terreus로부터 생산하기 위해 최적의 탄소원, 질소원, 인산염 및 아미노산을 선정하였다. 단일 탄소원에서는 글리세롤 45mL/L가 Lovastatin 256mg/L로 포도당 45g/L의 기본배지보다 약 3.5배 이상의 높은 Lovastatin 생산량을 나타내었다. 탄소원이 지방산 합성에 이용되는 것을 차단하고 Lovastatin으로의 합성을 촉진하기 위해 기름 증류를 탄소원으로 이용한 결과, 높은 Lovastatin 생산량과 균재량을 나타내었으나, 글리세롤 45mL/L가 Lovastatin 생산량이 낮았다 포도당 50g/L와 글리세롤 50mL/L를 혼합한 복합 탄소원이 Lovastatin 298mg/L로 기본배지에 비해 약 4배 이상의 가장 높은 Lovastatin 생산량을 나타냈었다. 질소원의 영향은 뚜렷하여 질소원에 따라 Lovastatin 생산량이 큰 차이를 나타내었으며, 그 중에서 peptonized milk가 가장 Lovastatin 생산량이 높았다. 인산염 중에서는 $K_2HPO_4$가 가장 높은 Lovastatin 생산량을 나타내었다. 이상에서 얻어진 최적 배지에 각종 아미노산을 첨가한 결과 L-hisbhine과 L-tryptophan이 가장 효과적이었으며, 최적 농도는 둘다 6g/L였다.
