Abstract
The biosynthetic gene cluster for tautomycin (TTM), a potent protein phosphatase (PP) inhibitor has recently been characterized. Inactivation of ttmM, which encodes a putative C3' hydroxylase, afforded mutant SB6005 which accumulated three new 3'-deshydroxy TTM analogs, supporting the function of TtmM and the previously proposed linear pathway for TTM biosynthesis. Bioassays reveal the importance of the C3' OH moiety in PP inhibition and that PP inhibition is not the exclusive mechanism driving TTM-induced cell death.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Furans / chemical synthesis
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Furans / chemistry
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Gene Expression Regulation, Bacterial / drug effects
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Lipids / chemical synthesis
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Lipids / chemistry
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Molecular Structure
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Multigene Family / drug effects
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Phosphoprotein Phosphatases / antagonists & inhibitors*
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Pyrans / chemical synthesis*
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Pyrans / chemistry
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Pyrans / pharmacology
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Spiro Compounds / chemical synthesis*
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Spiro Compounds / chemistry
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Spiro Compounds / pharmacology
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Streptomyces / genetics*
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Streptomyces / metabolism
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Structure-Activity Relationship
Substances
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Furans
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Lipids
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Pyrans
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Spiro Compounds
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tautomycin
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tautomycetin
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Phosphoprotein Phosphatases