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Construction of asm2 Deletion Mutant of Actinosynnema pretiosum and Medium Optimization for Ansamitocin P-3 Production Using Statistical Approach  

Bandi Srinivasulu (Institute for Marine Biosciences, NRC)
Kim Yoon-Jung (Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology)
Chang Yong-Keun (Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology)
Shang Guang-Dong (Department of Chemistry, University of Washington)
Yu Tin-Wein (Department of Chemistry, University of Washington)
Floss Heinz G. (Department of Chemistry, University of Washington)
Publication Information
Journal of Microbiology and Biotechnology / v.16, no.9, 2006 , pp. 1338-1346 More about this Journal
Abstract
Ansamitocin P-3 is a potent antitumor agent produced by A. pretiosum. A deletion mutant of A. pretiosum was constructed by deleting the asm2 gene, a putative transcriptional repressor. The deletion mutant showed a 9-fold enhanced ansamitocin P-3 productivity. The response surface method with central composite design was employed to further optimize the culture medium composition for ansamitocin P-3 production by the deletion mutant. The concentrations of four medium ingredients, dextrin, maltose, cotton seed flour, and yeast extract, which have been reported as major components for ansamitocin production, were optimized through a series of flask culture experiments. The optimum concentrations of the selected factors were found to be dextrin 6.0%; maltose 3.0%; cotton seed flour 0.53%; and yeast extract 0.45%. The maximum titer of ansamitocin P-3 was 78.3 mg/l with the optimized composition, about 15-folds higher than the unoptimized titer of 5.0 mg/l obtained with YMG medium.
Keywords
asm2 deletion mutant of Actinosynnema pretiosum; ansamitocin P-3 production; medium optimization; central composite design; response surface method;
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