Functions and properties of citrate lyase beta-subunit-like proteins
Final Report Abstract
The function of many proteins encoded in the genomes is unknown even for best studied model organisms like Eschreichia coli or Salmonella enterica. In this project, we studied the functions of homologs of citrate lyase β-subunit-like (CitE-like) proteins present in genomes of bacteria and archaea. Here we show that these proteins play a key role in various metabolic processes. In haloarchaea, they participate in acetate assimilation and in a modified leucine degradation pathway. In pathogens, they are involved in the degradation of itaconate. This compound has a dual role in metabolism of Salmonella Typhimurium. From one side, itaconate inhibits enzymes of the citric acid cycle and the glyoxylate bypass, succinate dehydrogenase and isocitrate lyase, and down-regulates the synthesis of anaplerotic enzymes, thus disrupting the growth. On the other hand, itaconate appears to be an important carbon source for S. Typhimurium during systemic infection, providing carbon and energy source to the pathogen. Our work not only revealed new enzymes and metabolic pathways functioning in various microorganisms (including important human pathogens), but also showed unexpected connection between microbial central metabolism and pathogenicity.
Publications
- Bacterial itaconate degradation promotes pathogenicity. Nat Chem Biol. 2014 10(5):371-377
Sasikaran J, Ziemski M, Zadora PK, Fleig A, Berg IA
(See online at https://doi.org/10.1038/nchembio.1482) - Unfamiliar metabolic links in the central carbon metabolism. J Biotechnol. 2014 192 Pt B:314-322
Fuchs G, Berg IA
(See online at https://doi.org/10.1016/j.jbiotec.2014.02.015) - Mesaconase activity of class I fumarase contributes to mesaconate utilization by Burkholderia xenovorans. Appl Environ Microbiol. 2015 81(16):5632-5638
Kronen M, Sasikaran J, Berg IA
(See online at https://doi.org/10.1128/AEM.00822-15) - Mesaconase/fumarase FumD in Escherichia coli O157:H7 and promiscuity of Escherichia coli class I fumarases FumA and FumB. PLoS One. 2015 10(12):e0145098
Kronen M, Berg IA
(See online at https://doi.org/10.1371/journal.pone.0145098) - Malate synthase and β-methylmalyl coenzyme A lyase reactions in the methylaspartate cycle in Haloarcula hispanica. J Bacteriol. 2017 199(4). pii: e00657-16
Borjian F, Han J, Hou J, Xiang H, Zarzycki J, Berg IA
(See online at https://doi.org/10.1128/JB.00657-16)
