Abstract
Activation of the polycyclic polyketide prenyltransferase (pcPTase)-containing silent clusters in Aspergillus fumigatus and Neosartorya fischeri led to isolation of a new metabolite neosartoricin (3). The structure of 3 was solved by X-ray crystallography and NMR to be a prenylated anthracenone. 3 exhibits T-cell antiproliferative activity with an IC(50) of 3 μM, suggestive of a physiological role as an immunosuppressive agent.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Aspergillus fumigatus / chemistry
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Aspergillus fumigatus / enzymology
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Aspergillus fumigatus / genetics*
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Crystallography, X-Ray
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Dimethylallyltranstransferase / metabolism
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Fungi / genetics
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Fungi / metabolism
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Genome*
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HeLa Cells
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Humans
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Immunosuppressive Agents / chemistry
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Immunosuppressive Agents / isolation & purification*
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Immunosuppressive Agents / pharmacology
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Macrophages / drug effects
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Mice
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Molecular Conformation
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Neosartorya / genetics*
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Neosartorya / metabolism
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Nuclear Magnetic Resonance, Biomolecular
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Polyketides / chemistry
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Polyketides / isolation & purification*
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Polyketides / pharmacology
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Prenylation
Substances
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Immunosuppressive Agents
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Polyketides
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Dimethylallyltranstransferase