DesT Coordinates the Expression of Anaerobic and Aerobic Pathways for Unsaturated Fatty Acid Biosynthesis in Pseudomonas aeruginosa

Abstract

The fabA and fabB genes are responsible for anaerobic unsaturated fatty acid formation in Pseudomonas aeruginosa. Expression of the fabAB operon was repressed by exogenous unsaturated fatty acids, and DNA sequences upstream of the translational start site were used to affinity purify DesT. The single protein interaction with the fabAB promoter detected in wild-type cell extracts was absent in the desT deletion strain, as was the repression of fabAB expression by unsaturated fatty acids. Thus, DesT senses the overall composition of the acyl-coenzyme A pool to coordinate the expression of the operons for the anaerobic (fabAB) and aerobic (desCB) pathways for unsaturated fatty acid synthesis.

Structural Basis for the Transcriptional Regulation of Heme Homeostasis in Lactococcus lactis

“…Although these TFRs bind different ligands (many structurally unrelated compounds such as ethidium, proflavin, and rhodamine 6G for AcrR (36), saturated fatty acid-CoA and unsaturated fatty acid-CoA for DesT (39,40), and numerous structurally dissimilar monovalent and bivalent cationic and lipophilic compounds for QacR (41,42)), their ligand-binding cavities are similarly positioned in the ligand-binding domain (28). Ligand binding results in a conformational change of the DNA-binding domain, for which the relocation of ␣6 helix upon ligand binding induces a pendulum-like motion of the DNA-binding domain in TFRs including TetR (43), QacR (41), and DesT (39).…”

“…The closest structural homologues of apoHrtR and holo-HrtR were identified using the DALI server (35). (36 -38), DesT (39,40) and QacR (41,42).…”

Bacterial lipids: Metabolism and membrane homeostasis

“…The expression of fabAB and desBC is controlled by the DesT repressor [309,310]. DesT is a TetR family transcription factor and functions to sense the overall fatty acid composition of the acyl-CoA pools.…”

“…DesT is a TetR family transcription factor and functions to sense the overall fatty acid composition of the acyl-CoA pools. DesT binds saturated and unsaturated acyl-CoAs with equal affinity but binding to DNA is enhanced when DesT is bound to an unsaturated acyl-CoA and perturbed when DesT is bound to a saturated acyl-CoA [309,310]. This allows P. aeruginosa to respond to the availability of exogenous saturated and unsaturated fatty acids and adjust gene expression to maintain a constant membrane fluidity.…”

Phosphatidic acid synthesis in bacteria

“…Saturated acyl-CoA binding to DesT causes dissociation from the promoter to increase desCB expression, while unsaturated acyl-CoA binding to DesT triggers tighter promoter association and strong repression. DesT also regulates fabAB expression in P. aeruginosa to coordinate aerobic and anaerobic pathways for unsaturated fatty acid formation [61]. The DesT structures provide a striking example of how these transcriptional regulators sense the conformation of fatty acids to maintain membrane homeostasis [62].…”