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Antimicrobial Agents and Chemotherapy, March 2000, p. 647-650, Vol. 44, No. 3
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

Seiji Kobayashi, Tomohisa Kuzuyama, and Haruo Seto*

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.


* 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.


Antimicrobial Agents and Chemotherapy, March 2000, p. 647-650, Vol. 44, No. 3
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Pakhomova, S., Bartlett, S. G., Augustus, A., Kuzuyama, T., Newcomer, M. E. (2008). Crystal Structure of Fosfomycin Resistance Kinase FomA from Streptomyces wedmorensis. J. Biol. Chem. 283: 28518-28526 [Abstract] [Full Text]  
  • Shimizu, M., Shigenobu, F., Miyakozawa, I., Nakamura, A., Nakazawa, K., Suzuki, M., Mizukoshi, S., O'Hara, K., Sawai, T., Chemistry, D. o. M. (2000). Novel Fosfomycin Resistance of Pseudomonas aeruginosa Clinical Isolates Recovered in Japan in 1996. Antimicrob. Agents Chemother. 44: 2007-2008 [Full Text]