Generation of new benanomicin analogues by biotransformation using Escherichia coli expressing actinomycete cytochrome P450.
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.
Kumagai
Hiroyuki
H
Microbial Chemistry Research Center, Tokyo, Japan. kumagai@m-cleantec.com
Umekita
Maya
M
Sawa
Ryuichi
R
Takahashi
Yoshikazu
Y
Arisawa
Akira
A
Isshiki
Kunio
K
Nishimura
Yoshio
Y
Akamatsu
Yuzuru
Y
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
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)