본 연구는 Asp. terreus ATCC 20542 변이주로부터 lovastatin 생산용 seed culture의 대량제조를 위한 방법을 개발한 것이다. 배양체의 선발, 분석 및 최적 배양용기를 검토한 결과 대두를 이용하여 petri dish(${phi}150{ imes}20mm$)에 배양하였을 때 lovastatin의 생산성이 우수하였다. 포자의 발아 촉진을 위하여 대두에 Asp. terreus를 접종한 다음 열처리를 달리하여, 각 전배양체를 미강에 본배양하였다. 본배양액을 추출한 후 HPLC를 이용하여 lovastatin 생산량을 검토한 결과 $30^{circ}C$에서 1시간 동안 열처리한 전배양체가 본배양 12일째에 가장 높은 lovastatin 생산성을 보이며, in vitro assay 결과, 대두를 $30^{circ}C$에서 1시간 열처리하여 본배양하였을 경우에 HMG-CoA reductase가 82% 저해되는 것으로 나타났다. 따라서 기존의 포자현탁액 접종법보다 대두를 이용한 방법이 더욱 높은 HMG-CoA reductase 저해활성 및 배양시간의 단축성을 보여 산업화에 유리한 것으로 사료되었다.
Lovastatin (Mevinolin, Monacolin K) is a well-known drug for the therapy of hypercholesterolemia. It is an important fungal secondary metabolite as it inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase, EC 1.1.1.34) which catalyzes a major rate-limiting step in the biosynthesis of cholesterol. Both soybeans and black soybeans with Aspergillus terreus ATCC 20542 mutant were used as the seed culture for the mass production of lovastatin. The production of lovastatin in soybean seed culture of Asp. terreus was twofold compared to that of black soybean seed culture. The effect of two different vessels (petri dish and Erlenmeyer flask) on lovastatin production was also studied. The production of lovastatin on petri dish was tenfold to that of Erlenmeyer flask. Furthermore, the most lovastatin production on rice bran was achieved when the soybean seed culture was treated by heat shock at $30^{circ}C$ for 1 hour, representing 82% of HMG-CoA reductase inhibition in the koji extract. We estimated that the heat treated soybean seed culture could be a new method for the mass production of lovastatin.
