Structural insights into repression of the Pneumococcal fatty acid synthesis pathway by repressor FabT and co‐repressor acyl‐ACP

: The Streptococcus pneumoniae fatty acid synthesis (FAS) pathway is globally controlled at the transcriptional level by the repressor FabT and its co-repressor acyl carrier protein (acyl-ACP), the intermediate of phospholipid synthesis. Here, we report the crystal structure of FabT complexed with a 23-bp dsDNA, which indicates that FabT is a weak repressor with low DNA-binding affinity in the absence of acyl-ACP. Modification of ACP with a long-chain fatty acid is necessary for the formation of a stable complex with FabT, mimicked in vitro by cross-linking, which significantly elevates the DNA-binding affinity of FabT. Altogether, we propose a putative working model of gene repression under the double control of FabT and acyl-ACP, elucidating a distinct repression network for Pneumococcus to precisely coordinate FAS.