Monday, July 30, 2007
P8

Statistical medium optimization to enhance the production of rifamycin B by Amycolatopsis mediterranei S699

Feng Xu Ma, Jung Hun Kim, Sung Bae Kim, Yang-Gon Seo, and Chang-Joon Kim. Department of Chemical & Biological Engineering, Gyeongsang National University, 900 Gazwa-Dong, Jinju, 660-701, South Korea

Rifamycin B, the product of the fermentation, is used as a raw material for the synthesis of rifampicin, chemotherapeutic agents used for combating tuberculosis, leprosy and AIDS-related mycobacterial infections. The most efforts to improve the rifamycin B production were strain improvement by random mutagenesis. No systematic studies to choose suitable carbon/ nitrogen sources and to optimize their concentrations were reported. Recently, the biosynthesis of rifamycin has been studied extensively to develop new drug based on rifamycin molecular structure by combinatorial biosynthesis. However, the yield of metabolite intermediate is too low to be identified. Accordingly, development of optimal medium will be helpful to increase the yield of these intermediates.

Here we present the medium optimization by a Plackett-Burman design and by response surface methodology. Plackett-Burman design was used for screening of fifteen medium components including carbon and nitrogen sources by performing twenty experiments separately. The positive effect of corn steep liquor was found whereas malt extract and KH2PO4 showed negative effect. Malt extract and KH2PO4 were omitted and concentration effects of glucose, (NH4)2SO4, and corn steep liquor were investigated to decide concentration range of these components for central composite design. Corn steep liquor was essential but its concentration effect was not significant. Experiments using central composite design were performed to optimize concentrations of glucose, and (NH4)2SO4 at 10 g/L of corn steep liquor.


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