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Antimicrobial Agents and Chemotherapy, March 2000, p. 647-650, Vol. 44, No. 3
Institute of Molecular and Cellular
Biosciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
Received 11 August 1999/Returned for modification 9 November
1999/Accepted 16 December 1999
Together, the fomA and fomB genes in the
fosfomycin biosynthetic gene cluster of Streptomyces
wedmorensis confer high-level fosfomycin resistance on
Escherichia coli. To elucidate their functions, the
fomA and fomB genes were overexpressed in
E. coli and the gene products were characterized. The
recombinant FomA protein converted fosfomycin to fosfomycin
monophosphate, which was inactive on E. coli, in the
presence of a magnesium ion and ATP. On the other hand, the recombinant
FomB protein did not inactivate fosfomycin. However, a reaction mixture
containing FomA and FomB proteins converted fosfomycin to fosfomycin
monophosphate and fosfomycin diphosphate in the presence of ATP and a
magnesium ion, indicating that FomA and FomB catalyzed phosphorylations of fosfomycin and fosfomycin monophosphate, respectively. These results
suggest that the self-resistance mechanism of the fosfomycin-producing organism S. wedmorensis is mono- and diphosphorylation of
the phosphonate function of fosfomycin catalyzed by FomA and FomB.
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Characterization of the fomA and
fomB Gene Products from Streptomyces wedmorensis,
Which Confer Fosfomycin Resistance on Escherichia
coli
*
Corresponding author. Mailing address: Institute of
Molecular and Cellular Biosciences, University of Tokyo, Yayoi,
Bunkyo-ku, Tokyo 113-0032, Japan. Phone: 81-3-5841-7839. Fax:
81-3-5841-8485. E-mail:
haseto{at}imcbns.iam.u-tokyo.ac.jp.
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