Abstract
Chain armor against tumor cells: The oxazole side chain in the antimitotic agent rhizoxin S2 (1) was successfully replaced through mutasynthesis by using an engineered mutant impaired in heterocyclization. Incorporation of 12 non-natural surrogates into fully processed rhizoxin analogues revealed a remarkable substrate flexibility of the PKS-NRPS hybrid.
MeSH terms
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Amino Acid Sequence
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Antibiotics, Antineoplastic / chemistry
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Antibiotics, Antineoplastic / metabolism*
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Burkholderia / chemistry
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Burkholderia / enzymology*
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Burkholderia / genetics*
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Burkholderia / metabolism
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Genes, Fungal
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Genetic Loci
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Macrolides / chemistry
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Macrolides / metabolism*
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Molecular Sequence Data
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Mutation
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Oxazoles / chemistry
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Oxazoles / metabolism*
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Peptide Synthases / genetics
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Peptide Synthases / metabolism
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Polyketide Synthases / genetics
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Polyketide Synthases / metabolism
Substances
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Antibiotics, Antineoplastic
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Macrolides
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Oxazoles
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Polyketide Synthases
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rhizoxin
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Peptide Synthases