title: Production of human metabolites of cyclosporin A, AM1, AM 4 N and AM 9, by microbial conversion.
abstract: In humans, cyclosporin A (CyA) is primarily metabolized to two hydroxylated (AM1 and AM 9) and one N-demethylated (AM 4 N) derivative. To produce these derivatives, 1237 actinomycetes were screened for their ability to convert CyA. Among them, 89 strains (7.2%) produced these derivatives from CyA. Finally, Dactylosporangium variesporum IFO 14104, Actinoplanes sp. ATCC 53771 and Streptosporangium sp. AF 935 were selected for the production of AM1, AM 4 N, and AM 9, respectively. Composition of the production medium and the incubation period with CyA were important for obtaining a high yield of CyA derivatives. Large-scale microbial conversion of CyA (1.5 g) using a 30-l jar fermentor yielded 288 mg of AM1 (19.2%), 147 mg of AM 4 N (9.8%) and 115 mg of AM 9 (7.7%).
authors.affiliation: Bioresource Laboratories, Mercian Corp., 1808 Nakaizumi, Iwata-shi, Shizuoka 438-0078, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ohta
authors.forename: Hitosi
authors.initials: H
authors.lastname: Agematu
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamada
authors.forename: Katsura
authors.initials: K
authors.lastname: Kaneko
authors.forename: Toshio
authors.initials: T
authors.lastname: Tsuchida
mesh_terms: D039903:Actinobacteria / Q000302:isolation & purification* / Q000378:metabolism*; D016572:Cyclosporine / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D012988:Soil Microbiology; D013045:Species Specificity
chemical_list: D016572:Cyclosporine