title: Generation of new benanomicin analogues by biotransformation using Escherichia coli expressing actinomycete cytochrome P450.
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.
authors.affiliation: Microbial Chemistry Research Center, Tokyo, Japan. kumagai@m-cleantec.com
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kumagai
authors.forename: Maya
authors.initials: M
authors.lastname: Umekita
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sawa
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Akira
authors.initials: A
authors.lastname: Arisawa
authors.forename: Kunio
authors.initials: K
authors.lastname: Isshiki
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Akamatsu
mesh_terms: D039903:Actinobacteria / Q000201:enzymology* / Q000235:genetics; D018943:Anthracyclines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D005658:Fungi / Q000187:drug effects; D014162:Transfection; D000095643:Pradimicins and Benanomicins
chemical_list: D018943:Anthracyclines; D000935:Antifungal Agents; D003577:Cytochrome P-450 Enzyme System; C056805:benanomicin A; D000095643:Pradimicins and Benanomicins; C105438:cytochrome P-450 CYP105C1 (Streptomyces griseolus)