Lee Mi-Jin, Lee Han-Na, Han Kyubeom, Kim Eung-Soo
Hanson Biotech Co., Ltd., 201 IACRI, Han Nam University, Daejeon 306-791, Korea.
J Microbiol Biotechnol. 2008 May;18(5):913-7.
The cyclic undecapeptide, cyclosporin A (CyA), is one of the most commonly prescribed immunosuppressive drugs. It is generated nonribosomally from a multifunctional cyclosporin synthetase enzyme complex by the filamentous fungus Tolypocladium niveum. In order to maximize the production of CyA by wild-type T. niveum (ATCC 34921), each of three culture stages (sporulation culture, growth culture, and production culture) were sequentially optimized. Among the three potential sporulation media, the SSMA medium generated the highest numbers of T. niveum spores. The SSM and SM media were then selected as the optimal growth and production culture media, respectively. The addition of valine and fructose to the SM production medium was also determined to be crucial for CyA biosynthesis. In this optimized three-stage culture system, 3% of the spore inoculum generated the highest level of CyA productivity in a 15-day T. niveum production culture, thereby implying that the determination of an appropriate size of T. niveum spore inoculum plays a critical role in the maximization of CyA production.
环状十一肽环孢菌素A（CyA）是最常用的免疫抑制药物之一。它由丝状真菌雪白丝枝霉通过多功能环孢菌素合成酶复合物非核糖体合成。为了使野生型雪白丝枝霉（ATCC 34921）的CyA产量最大化，依次对三个培养阶段（孢子形成培养、生长培养和生产培养）进行了优化。在三种潜在的孢子形成培养基中，SSMA培养基产生的雪白丝枝霉孢子数量最多。然后分别选择SSM和SM培养基作为最佳生长培养基和生产培养基。还确定在SM生产培养基中添加缬氨酸和果糖对CyA生物合成至关重要。在这个优化的三阶段培养系统中，在15天的雪白丝枝霉生产培养中，3%的孢子接种量产生了最高水平的CyA生产力，这意味着确定合适大小的雪白丝枝霉孢子接种量对CyA产量最大化起着关键作用。
