Improvement of FR901379 production by mutant selection and medium optimization(BIOCHEMICAL ENGINEERING)
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概要
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FR901379 (WF11899A) is a novel echinocandin type of lipopeptide antibiotic produced by Coleophoma empetri F-11899. Micafungin (FK463) is derived from the chemical modification of deacylated FR901379. In the present paper, we performed seven generation's strain-breeding, beginning with a wild type, was performed. Selection medium for screening and production medium for high FR901379 production were designed. Sodium chloride content in the selection plate was affected to FR901379 production and shrinkage of the colony size was observed in high producing strains. As selection markers, large colony-shrinking rate and large inhibition circle in the agar-piece method using C. albicans was selected. Using CMA medium with high sodium chloride, 3 mutants, M-1 to M-3, have achieved a high FR901379 production and M-3 showed 5.0U/mL, while 1.0U/mL of production was achieved in wild type strain. A-2 medium supplemented with 6% of soluble starch as a carbon source and 0.6% of ammonium sulfate as nitrogen source was also further effective for mutant screening. The FR901379 production of mutant M-4 (fourth generation) increased until 16.0U/mL The concentration of the phosphate salt in the medium seemed to inhibit the growth so as to extend the culture period. When the A-3 medium supplemented with low concentration of phosphate salt and magnesium sulfate as a sulfate source was designed and used, mutants with improved production were successively obtained. Finally, variant strain M-7 showed 30.0U/mL of production, which was about 30 times higher than that of the wild strain.
著者
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Kanda Munekazu
Fermentation and Biotechnology Laboratories, Astellas Pharma Inc.
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Tsuboi Masaru
Fermentation and Biotechnology Laboratories, Astellas Pharma Inc.
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Sakamoto Kazutoshi
Fermentation Research Laboratories, Astellas Pharma Inc.
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Shimizu Shiho
Fermentation and Biotechnology Laboratories, Astellas Pharma Inc.
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Yamashita Michio
Fermentation and Biotechnology Laboratories, Astellas Pharma Inc.
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Honda Hiroyuki
Department of Biotechnology, School of Engineering, Nagoya University
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Honda Hiroyuki
Department Of Biotechnology Graduate School Of Engineering Nagoya University:mext Innovative Researc
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Kanda Munekazu
Fermentation And Biotechnology Laboratories Astellas Pharma Inc.:(present Office) Fermentation Techn
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Honda Hiroyuki
Department Of Bioengineering Tokyo Institute Of Technology
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Honda Hiroyuki
Department Of Biotechnology School Of Engineering Nagoya University:mext Innovative Research Center
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Sakamoto Kazutoshi
Fermentation Research Laboratories Astellas Pharma Inc.
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Honda Hiroyuki
Department Of Cardiovascular Research R.i.e.m. Nagoya University
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Honda Hiroyuki
Graduate School Of Engineering Nagoya University
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Yamashita Michio
Fermentation And Biotechnology Laboratories Astellas Pharma Inc.
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Hosokawa Hiroyuki
Department Of Immunology Graduate School Of Medicine Chiba University
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Tsuboi Masaru
Fermentation And Biotechnology Laboratories Astellas Pharma Inc.
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Shimizu Shiho
Fermentation And Biotechnology Laboratories Astellas Pharma Inc.
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Hamada Hirobumi
Department Of Molecular Medicine Sapporo Medical University School Of Medicine
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Honda Hiroyuki
Department Of Anesthesia Niigata City General Hospital
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Yamashita Michio
Fermentation And Biotechnology Laboratories
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