Strain improvement of Lentzea sp. 7887 for higher yield per unit volume on hydroxylation of cyclosporine derivative FR901459 |
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Authors: | Tetsuya Yabutani Mami Tsujimoto Shunsuke Ohira Shiho Shimizu Hideo Nakano |
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Institution: | 1. Technology Product Management, Astellas Pharma Inc., Tokyo, Japan;2. Laboratory of Molecular Biotechnology, Division of Biotechnology, Department of Bioengineering Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan;3. Biotechnology Laboratory, Astellas Pharma Inc., Tsukuba, Japan;4. Technology Development, Toyama Technology Center, Astellas Pharma Tech Co. Ltd., Toyama, Japan;5. Laboratory of Molecular Biotechnology, Division of Biotechnology, Department of Bioengineering Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan |
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Abstract: | A Gram-positive bacterium Lentzea sp. 7887 hydroxylates a cyclosporine derivative FR901459 into AS1837812 (9-hydroxide), which is an important intermediate of candidate drugs that target the hepatitis C virus. We screened a UV-induced mutant, named M-1, which showed about 1.2-fold higher conversion yields, 2-fold higher substrate concentrations (3.69 mM), and 2.5-fold higher yield per unit volume than the wild-type strain. |
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Keywords: | mutation bioconversion Lentzea pilot scale cyclosporine derivative |
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