Crystal Structure of the E. coli AcpP=FabB Complex

The acyl carrier protein (ACP) plays a central role in both primary and secondary metabolism. In E. coli, the ACP AcpP is responsible for transporting a growing fatty acid during biosynthesis. In different biosynthetic pathways including fatty acid biosynthesis (FA), AcpP interacts with at least 20 enzymes while it delivers intermediates into different active sites. The interactions between AcpP and its partner enzymes are transient, which has hampered efforts to gain structural knowledge of how AcpP interacts with its partner enzymes. In order to gain a better understanding of how AcpP interacts with the ketosynthase (KS) FabB during E. coli FA biosynthesis, an enzyme-specific mechanism-based crosslinking strategy was used. By applying this method, a stable crosslinked AcpP=FabB complex was purified, crystallized, and the crystal structure determined to 2.4 Å. The AcpP=FabB structure is the first structure of an ACP/KS complex and reveals important residues for complex formation. This work represents a major breakthrough in understanding type II FA biosynthesis, and provides a structural basis for engineering the production of pharmaceuticals and biofuels in E. coli.