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      Generation of new benanomicin analogues by biotransformation using Escherichia coli expressing actinomycete cytochrome P450.

      The Journal of antibiotics
      Actinobacteria, enzymology, genetics, Anthracyclines, chemistry, metabolism, pharmacology, Antifungal Agents, Biotransformation, Cytochrome P-450 Enzyme System, Escherichia coli, Fungi, drug effects, Transfection

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          Abstract

          Benanomicins were found as antifungal antibiotics from the culture of an actinomycete with potent antifungal activities in vitro and in vivo. We aimed to generate derivatives superior to benanomicin A by biotransformation using Escherichia coli constructed with bacterial P450 expression system. We found transformation of benanomicin A into two derivatives, 10-hydroxybenanomicin A and 11-O-demethylbenanomicin A by one of the P450-expressed strains which harbored a plasmid carrying a CYP105C1-homologous gene. Unexpectedly, the biotransformed compounds showed weak antifungal activities in vitro compared with those of benanomicin A.

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