The fatty acid biosynthesis pathway (FAS) was a fundamental procedure to generate a diversity of lipid components for cellular metabolism in bacteria, while the mechanism of substrate recognition remains unclear. The beta-hydroxyacyl-acyl carrier protein dehydratase hexamer (FabZ) is an essential module in the elongation cycle of type-II FAS, catalyzing the dehydration of beta-hydroxyacyl-lipid substrate carried by the holo form acyl carrier protein (holo-ACP). We previously elucidated an alternating seesaw-like ACP loading manner within a FabZ dimer subunits, mediated by a front-door residue Tyrosine (Tyr100). Here, we demonstrated that a back-door residue Phenylalanine (Phe83) of FabZ regulates the stepwise hexameric loading of ACP. Our finding represents clues as to the dynamic ACP recognition and catalysis mechanism of dehydratase in fatty acid biosynthesis, and provides critical information for developing antimicrobials targeting the dehydratase module in fatty acid biosynthesis pathway.

Acyl carrier protein; Dehydratase; Dynamic ACP regulation; Fatty acid biosynthesis; Helicobacter pylori

Shandong University