FabA

FabA is a bacterial enzyme that plays a central role in type II fatty acid biosynthesis (FAS II). It is a bifunctional protein with beta-hydroxyacyl-ACP dehydratase activity and an isomerase activity. The dehydratase reaction converts 3-hydroxyacyl-ACP to trans-2-enoyl-ACP, while the isomerase converts certain trans-2-enoyl-ACP intermediates into cis-3-enoyl-ACP. This cis-3-enoyl-ACP is a key precursor for the production of monounsaturated fatty acids, enabling membrane fluidity when unsaturated lipids are required.

In Escherichia coli and many other Gram-negative bacteria, FabA works in concert with FabB, the elongating beta-ketoacyl-ACP synthase, to channel intermediates toward unsaturated fatty acid synthesis. The enzyme is typically a soluble cytosolic protein of about 18–20 kDa per subunit and functions as a dimer. It acts on acyl carrier protein (ACP)-bound intermediates, interacting with the pantetheine arm of ACP to carry out its catalysis.

Genetically, FabA is encoded by the fabA gene and is part of the broader fatty acid biosynthesis regulon. Its expression and activity respond to cellular needs for membrane composition and environmental conditions. Structurally, FabA belongs to the family of dehydratases associated with the FAS II system, sharing features with related enzymes that catalyze dehydration and isomerization steps during fatty acid elongation.

FabA is of interest as a potential target for antibiotics that disrupt bacterial membrane lipid synthesis. Its distribution is most prominent among Gram-negative bacteria, with variations in unsaturated fatty acid pathways observed across species.