Production of human metabolites of cyclosporin A, AM1, AM 4 N and AM 9, by microbial conversion

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. F...

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Bibliographic Details
Published in:Journal of bioscience and bioengineering 2005-04, Vol.99 (4), p.390-395
Main Authors: Ohta, Kazuo, Agematu, Hitosi, Yamada, Tomoya, Kaneko, Katsura, Tsuchida, Toshio
Format: Article
Language:English
Subjects:
Actinobacteria - isolation & purification
Actinobacteria - metabolism
Cyclosporine - chemistry
Cyclosporine - isolation & purification
Cyclosporine - metabolism
Humans
Soil Microbiology
Species Specificity
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Summary: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%).
ISSN:1389-1723