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Journal of Bacteriology, January 2009, p. 52-64, Vol. 191, No. 1
0021-9193/09/$08.00+0     doi:10.1128/JB.01175-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Comparative Genomics of Regulation of Fatty Acid and Branched-Chain Amino Acid Utilization in Proteobacteria{triangledown} ,{dagger}

Alexey E. Kazakov,1,{ddagger} Dmitry A. Rodionov,1,2,{ddagger}* Eric Alm,3,4 Adam Paul Arkin,4,5,6 Inna Dubchak,4,5 and Mikhail S. Gelfand1,7

Institute for Information Transmission Problems (the Kharkevich Institute), RAS, Moscow, Russia,1 Burnham Institute for Medical Research, La Jolla, California,2 Departments of Biological Engineering and Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts,3 Virtual Institute of Microbial Stress and Survival, Lawrence Berkeley National Laboratory, Berkeley, California,4 Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California,5 Department of Bioengineering, University of California, Berkeley, California,6 Faculty of Bioengineering and Bioinformatics, Moscow State University, Moscow, Russia7

Received 20 August 2008/ Accepted 12 September 2008

Bacteria can use branched-chain amino acids (ILV, i.e., isoleucine, leucine, valine) and fatty acids (FAs) as sole carbon and energy sources converting ILV into acetyl-coenzyme A (CoA), propanoyl-CoA, and propionyl-CoA, respectively. In this work, we used the comparative genomic approach to identify candidate transcriptional factors and DNA motifs that control ILV and FA utilization pathways in proteobacteria. The metabolic regulons were characterized based on the identification and comparison of candidate transcription factor binding sites in groups of phylogenetically related genomes. The reconstructed ILV/FA regulatory network demonstrates considerable variability and involves six transcriptional factors from the MerR, TetR, and GntR families binding to 11 distinct DNA motifs. The ILV degradation genes in gamma- and betaproteobacteria are regulated mainly by a novel regulator from the MerR family (e.g., LiuR in Pseudomonas aeruginosa) (40 species); in addition, the TetR-type regulator LiuQ was identified in some betaproteobacteria (eight species). Besides the core set of ILV utilization genes, the LiuR regulon in some lineages is expanded to include genes from other metabolic pathways, such as the glyoxylate shunt and glutamate synthase in Shewanella species. The FA degradation genes are controlled by four regulators including FadR in gammaproteobacteria (34 species), PsrA in gamma- and betaproteobacteria (45 species), FadP in betaproteobacteria (14 species), and LiuR orthologs in alphaproteobacteria (22 species). The remarkable variability of the regulatory systems associated with the FA degradation pathway is discussed from functional and evolutionary points of view.


* Corresponding author. Mailing address: Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037. Phone: (858) 646-3100. Fax: (858) 795-5249. E-mail: rodionov{at}burnham.org

{triangledown} Published ahead of print on 26 September 2008.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

{ddagger} A.E.K. and D.A.R. contributed equally to the paper.


Journal of Bacteriology, January 2009, p. 52-64, Vol. 191, No. 1
0021-9193/09/$08.00+0     doi:10.1128/JB.01175-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.




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  • Novichkov, P. S., Laikova, O. N., Novichkova, E. S., Gelfand, M. S., Arkin, A. P., Dubchak, I., Rodionov, D. A. (2009). RegPrecise: a database of curated genomic inferences of transcriptional regulatory interactions in prokaryotes. Nucleic Acids Res 0: gkp894v1-gkp894 [Abstract] [Full Text]