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Spore Inoculum Optimization to Maximize Cyclosporin A Production in Tolypocladium niveum  

Lee, Mi-Jin (Department of Biological Engineering, Inha University)
Lee, Han-Na (Department of Biological Engineering, Inha University)
Han, Kyu-Boem (Hanson Biotech Co., Ltd.)
Kim, Eung-Soo (Department of Biological Engineering, Inha University)
Publication Information
Journal of Microbiology and Biotechnology / v.18, no.5, 2008 , pp. 913-917 More about this Journal
Abstract
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.
Keywords
Tolypocladium niveum; cyclosporin A; spore inoculum;
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Times Cited By KSCI : 6  (Citation Analysis)
Times Cited By Web Of Science : 4  (Related Records In Web of Science)
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