Perturbation of the metabolic network in Salmonella enterica reveals cross-talk between coenzyme A and thiamine pathways.
PLoS One
; 13(5): e0197703, 2018.
Article
de En
| MEDLINE
| ID: mdl-29791499
ABSTRACT
Microorganisms respond to a variety of metabolic perturbations by repurposing or recruiting pathways to reroute metabolic flux and overcome the perturbation. Elimination of the 2-dehydropantoate 2-reductase, PanE, both reduces total coenzyme A (CoA) levels and causes a conditional HMP-P auxotrophy in Salmonella enterica. CoA or acetyl-CoA has no demonstrable effect on the HMP-P synthase, ThiC, in vitro. Suppressors aimed at probing the connection between the biosynthesis of thiamine and CoA contained mutations in the gene encoding the ilvC transcriptional regulator, ilvY. These mutations may help inform the structure and mechanism of action for the effector-binding domain, as they represent the first sequenced substitutions in the effector-binding domain of IlvY that cause constitutive expression of ilvC. Since IlvC moonlights as a 2-dehydropantoate 2-reductase, the resultant increase in ilvC transcription increased synthesis of CoA. This study failed to identify mutations overcoming the need for CoA for thiamine synthesis in S. enterica panE mutants, suggesting that a more integrated approach may be necessary to uncover the mechanism connecting CoA and ThiC activity in vivo.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Thiamine
/
Coenzyme A
/
Salmonella enterica
/
Voies et réseaux métaboliques
Langue:
En
Journal:
PLoS One
Sujet du journal:
CIENCIA
/
MEDICINA
Année:
2018
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique