Spore inoculum optimization to maximize cyclosporin A production in Tolypocladium niveum.
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.
Lee
Mi-Jin
MJ
Hanson Biotech Co., Ltd., 201 IACRI, Han Nam University, Daejeon 306-791, Korea.
Lee
Han-Na
HN
Han
Kyubeom
K
Kim
Eung-Soo
ES
D018533:Biomass; D003470:Culture Media / Q000737:chemistry; D016572:Cyclosporine / Q000378:metabolism*; D005285:Fermentation; D006999:Hypocreales / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D007218:Industrial Microbiology; D025282:Mycelium / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D013172:Spores, Fungal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*
D003470:Culture Media; D016572:Cyclosporine