Abstract
The Fe(II) and α-ketoglutarate-dependent hydroxylase FrbJ was previously demonstrated to utilize FR-900098 synthesizing a second phosphonate FR-33289. Here we assessed its ability to hydroxylate other possible substrates, generating a library of potential antimalarial compounds. Through a series of bioassays and in vitro experiments, we identified two new antimalarials.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Antimalarials / chemistry*
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Antimalarials / metabolism
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Antimalarials / pharmacology
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Bacterial Proteins / metabolism*
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Ferrous Compounds / chemistry*
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Fosfomycin / analogs & derivatives
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Fosfomycin / biosynthesis
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Fosfomycin / chemistry
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Fosfomycin / pharmacology
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Ketoglutaric Acids / chemistry*
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Mixed Function Oxygenases / metabolism*
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Plasmodium falciparum / drug effects
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Plasmodium falciparum / enzymology
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Streptomyces / enzymology
Substances
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Antimalarials
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Bacterial Proteins
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Ferrous Compounds
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Ketoglutaric Acids
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Fosfomycin
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fosmidomycin
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3-(N-acetyl-N-hydroxy)aminopropylphosphonic acid
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FR 33289
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Mixed Function Oxygenases