title: Strain improvement of Lentzea sp. 7887 for higher yield per unit volume on hydroxylation of cyclosporine derivative FR901459.
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.
authors.affiliation: a Technology Product Management , Astellas Pharma Inc. , Tokyo , Japan.|d Laboratory of Molecular Biotechnology, Division of Biotechnology, Department of Bioengineering Science , Graduate School of Bioagricultural Sciences, Nagoya University , Nagoya , Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yabutani
authors.affiliation: b Biotechnology Laboratory , Astellas Pharma Inc. , Tsukuba , Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Tsujimoto
authors.affiliation: b Biotechnology Laboratory , Astellas Pharma Inc. , Tsukuba , Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ohira
authors.affiliation: c Technology Development, Toyama Technology Center , Astellas Pharma Tech Co. Ltd., Toyama , Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: d Laboratory of Molecular Biotechnology, Division of Biotechnology, Department of Bioengineering Science , Graduate School of Bioagricultural Sciences, Nagoya University , Nagoya , Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Nakano
mesh_terms: D039903:Actinobacteria / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D000998:Antiviral Agents / Q000378:metabolism*; D001711:Biotransformation; D016572:Cyclosporine / Q000378:metabolism*; D006900:Hydroxylation; D060847:Metabolic Engineering / Q000379:methods; D009154:Mutation / Q000528:radiation effects*; D012641:Selection, Genetic; D013379:Substrate Specificity; D014466:Ultraviolet Rays
chemical_list: D000998:Antiviral Agents; C085611:FR 901459; D016572:Cyclosporine
keywords: Lentzea; bioconversion; cyclosporine derivative; mutation; pilot scale