Hydroxyornithine transformylase (PvdF) (PvdF)

PvdF (Hydroxyornithine transformylase) is a critical enzyme in the biosynthesis of pyoverdine, the primary siderophore produced by the opportunistic pathogen Pseudomonas aeruginosa. It catalyzes the formylation of L-N5-hydroxyornithine to L-N5-formyl-N5-hydroxyornithine, utilizing N10-formyltetrahydrofolate as the formyl donor. This enzymatic step is essential for the production of the hydroxamate ligands that allow pyoverdine to scavenge iron from the host environment with high affinity. Since iron is a vital nutrient for bacterial growth and a key signal for the expression of multiple virulence factors, PvdF is considered a promising therapeutic target for anti-virulence strategies. Inhibition of PvdF leads to a significant reduction in pyoverdine production, thereby impairing the bacterium's ability to survive in iron-depleted host environments and reducing its overall pathogenicity. While no clinical drugs currently target PvdF, experimental studies have identified natural compounds and synthetic inhibitors that can disrupt this pathway, offering a potential avenue for treating multi-drug resistant P. aeruginosa infections. Targeting PvdF offers a strategy to combat infections by attenuating bacterial virulence rather than directly killing the pathogen, which may potentially slow the development of antimicrobial resistance.

Other names

PvdFHydroxyornithine transformylaseFormyltransferase PvdFL-N5-hydroxyornithine transformylase

Catalyzes the formylation of L-N5-hydroxyornithine to L-N5-formyl-N5-hydroxyornithine using N10-formyltetrahydrofolate as a formyl donor, thereby providing essential precursors for pyoverdine synthesis.