3-hydroxyacyl-[acyl-carrier-protein] dehydratase FabZ (FabZ)

3-hydroxyacyl-[acyl-carrier-protein] dehydratase FabZ (commonly abbreviated as FabZ) is an enzyme universally expressed in the bacterial type II fatty acid synthase (FASII) pathway[6][8]. It catalyzes the dehydration of (3R)-hydroxyacyl-ACP intermediates to form trans-2-acyl-ACPs, a key step in elongating fatty acids that are vital for cell membrane biosynthesis[1][3][6]. FabZ acts on both short- and long-chain saturated and unsaturated fatty acyl substrates, in contrast to its isoform FabA, which has more substrate selectivity and an additional isomerization function[3][4][5]. FabZ forms functional hexamers (or trimer of dimers), with a conserved His/Glu catalytic dyad deeply buried in the active site tunnel[6]. Loss of FabZ function impairs bacterial growth and virulence; for instance, in Toxoplasma gondii, FabZ deletion reduces pathogenicity[7]. Because human fatty acid synthesis uses a different, type I FAS system, FabZ and other FASII enzymes are considered attractive antibiotic targets, with experimental inhibitors under investigation[6][8]. No clinical drugs specifically target FabZ to date, but its essentiality in many pathogens underpins ongoing drug discovery efforts.

Other names

3R-hydroxyacyl-[acyl-carrier-protein] dehydratase(3R)-hydroxymyristoyl-ACP dehydratasebeta-hydroxyacyl-ACP dehydratase3-hydroxyacyl-ACP dehydratase

Inhibition of FabZ leads to disruption of bacterial fatty acid synthesis, compromising membrane formation and bacterial viability