Combined, Functional Genomic-Biochemical Approach To Intermediary Metabolism: Interaction Of Acivicin, A Glutamine Amidotransferase Inhibitor, With Escherichia Coli K-12

Authors

D. R. Smulski
L. L. Huang
M. P. McCluskey
M. J. Gladnick Reeve
Amy Cheng Vollmer, Swarthmore CollegeFollow
T. K. Van Dyk
R. A. LaRossaFollow

Document Type

Article

Publication Date

6-1-2001

Published In

Journal Of Bacteriology

Abstract

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.

Comments

This work is freely available courtesy of American Society for Microbiology.

Recommended Citation

D. R. Smulski, L. L. Huang, M. P. McCluskey, M. J. Gladnick Reeve, Amy Cheng Vollmer, T. K. Van Dyk, and R. A. LaRossa. (2001). "Combined, Functional Genomic-Biochemical Approach To Intermediary Metabolism: Interaction Of Acivicin, A Glutamine Amidotransferase Inhibitor, With Escherichia Coli K-12". Journal Of Bacteriology. Volume 183, Issue 11. 3353-3364. DOI: 10.1128/JB.183.11.3353-3364.2001
https://works.swarthmore.edu/fac-biology/16