Generation of Novel Rapamycin Structures by Microbial Manipulations

A new rapamycin producing culture was isolated and designated as Actinoplanes sp. N902-109. The addition of a cytochrome P-450 inhibitor and precursor feeding using this culture, and biotransformation approaches generated new rapamycin analogs with modifications at C-4, C-9, C-16, C-27, C-28 and/or...

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Bibliographic Details
Published in:Journal of antibiotics 1995/07/25, Vol.48(7), pp.657-666
Main Authors: NLSHIDA, HLROYUKI, SAKAKIBARA, TATSUO, AOKI, FUKUMATSU, SAITO, TOSHIYUKI, ICHIKAWA, KATSUOMI, INAGAKI, TAISUKE, KOJIMA, YASUHIRO, YAMAUCHI, YUJI, HUANG, LIANG H., GUADLIANA, MARK A., KANEKO, TAKUSHI, KOJIMA, NAKAO
Format: Article
Language:English
Subjects:
Actinomycetales - classification
Actinomycetales - metabolism
Actinoplanes
Antifungal Agents - chemistry
Antifungal Agents - isolation & purification
Antifungal Agents - pharmacology
Biological and medical sciences
Biotransformation
Cytochrome P-450 Enzyme Inhibitors
Fermentation
Humans
Immunomodulators
Immunosuppressive Agents - chemistry
Immunosuppressive Agents - isolation & purification
Immunosuppressive Agents - pharmacokinetics
Lymphocytes - drug effects
Medical sciences
Molecular Structure
Pharmacology. Drug treatments
Polyenes - chemistry
Polyenes - isolation & purification
Polyenes - pharmacokinetics
Sirolimus
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Summary:A new rapamycin producing culture was isolated and designated as Actinoplanes sp. N902-109. The addition of a cytochrome P-450 inhibitor and precursor feeding using this culture, and biotransformation approaches generated new rapamycin analogs with modifications at C-4, C-9, C-16, C-27, C-28 and/or C-39. The immunosuppressive activity of the resulting analogs was established in the mixed lymphocyte reaction assay.
ISSN:0021-8820
1881-1469
DOI:10.7164/antibiotics.48.657