3-hydroxydecanoyl-[acyl-carrier-protein] dehydratase (FabA) (FabA)

3-hydroxydecanoyl-[acyl-carrier-protein] dehydratase (FabA) is a dual-function enzyme essential for the Type II fatty acid synthesis (FAS II) pathway in many bacteria, including Escherichia coli [3, 6]. It plays a unique role by catalyzing both the dehydration of 3-hydroxydecanoyl-ACP to trans-2-decenoyl-ACP and the subsequent isomerization of this product to cis-3-decenoyl-ACP [6, 9]. This isomerization step is the critical branch point that allows the production of unsaturated fatty acids, which are vital for maintaining bacterial membrane fluidity and integrity [4, 6]. Because humans utilize a structurally distinct Type I fatty acid synthase (FAS I) system, FabA represents a highly selective target for the development of novel antibacterial agents [4]. Inhibitors such as the suicide substrate 3-decynoyl-N-acetylcysteamine and small molecules like NAS-91 effectively block this pathway, leading to bacterial cell death [6, 9]. Targeting FabA is particularly relevant for treating infections caused by Gram-negative pathogens, although the potential for resistance through mutations or the presence of the related enzyme FabZ remains a therapeutic challenge [6]. Overall, FabA is a well-validated target for narrow-spectrum antibiotic discovery aimed at disrupting bacterial lipid metabolism [4].

Other names

Beta-hydroxyacyl-ACP dehydratase3-hydroxydecanoyl-ACP dehydratase3-hydroxydecanoyl-ACP dehydraseHDDaseBeta-hydroxydecanoyl thioester dehydrase3-hydroxydecanoyl-ACP dehydratase/isomerase

Inhibition of the dehydration and isomerization of 3-hydroxydecanoyl-ACP, which blocks the synthesis of unsaturated fatty acids and disrupts bacterial membrane formation.