JB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Smulski, D. R.
Right arrow Articles by LaRossa, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Smulski, D. R.
Right arrow Articles by LaRossa, R. A.

 Previous Article  |  Next Article 

Journal of Bacteriology, June 2001, p. 3353-3364, Vol. 183, No. 11
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.11.3353-3364.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Combined, Functional Genomic-Biochemical Approach to Intermediary Metabolism: Interaction of Acivicin, a Glutamine Amidotransferase Inhibitor, with Escherichia coli K-12

Dana R. Smulski, Lixuan L. Huang, Michael P. McCluskey, Mary Jane Gladnick Reeve, Amy C. Vollmer,dagger Tina K. Van Dyk, and Robert A. LaRossa*

Biochemical Science and Engineering, Central Research and Development, DuPont Company, Wilmington, Delaware 19880-0173

Received 16 January 2001/Accepted 16 March 2001

Acivicin, a modified amino acid natural product, is a glutamine analog. Thus, it might interfere with metabolism by hindering glutamine transport, formation, or usage in processes such as transamidation and translation. This molecule prevented the growth of Escherichia coli in minimal medium unless the medium was supplemented with a purine or histidine, suggesting that the HisHF enzyme, a glutamine amidotransferase, was the target of acivicin action. This enzyme, purified from E. coli, was inhibited by low concentrations of acivicin. Acivicin inhibition was overcome by the presence of three distinct genetic regions when harbored on multicopy plasmids. Comprehensive transcript profiling using DNA microarrays indicated that histidine biosynthesis was the predominant process blocked by acivicin. The response to acivicin, however, was quite complex, suggesting that acivicin inhibition resonated through more than a single cellular process.

* Corresponding author. Mailing address: DuPont Company, Central Research and Development, Biochemical Science and Engineering, Experimental Station, P.O. Box 80173, Wilmington, DE 19880-0173. Phone: (302) 695-9264. Fax: (302) 695-9183. E-mail: Robert.A.LaRossa{at}usa.dupont.com.

dagger Present address: Department of Biology, Swarthmore College, Swarthmore, PA 19081-1390.

Journal of Bacteriology, June 2001, p. 3353-3364, Vol. 183, No. 11
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.11.3353-3364.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Appl. Environ. Microbiol. Infect. Immun. Eukaryot. Cell
Mol. Cell. Biol. J. Virol. Microbiol. Mol. Biol. Rev.
ALL ASM JOURNALS

Copyright © 2001 by the American Society for Microbiology. All rights reserved.