A Novel Gene Contributing to the Initiation of Fatty Acid Biosynthesis in Escherichia coli

Type II fatty acid biosynthesis in bacteria can be broadly classified into the initiation and elongation phases. The biochemical functions defining each step in the two phases have been studied in vitro. Among the beta-ketoacyl-acyl carrier protein (ACP) synthases, FabH catalyzes the initiation reaction, while FabB and FabF, which primarily catalyze the elongation reaction, can also drive initiation as side reactions. A role for FabB and FabF in the initiation of fatty acid biosynthesis would be supported by the viability of the Delta fabH mutant. In this study, we show that the Delta fabH and Delta yiiD mutations were synthetically lethal and that Delta fabH Delta relA Delta spoT and Delta fabH Delta dksA synthetic lethality was rescued by the heterologous expression of yiiD. In the Delta fabH mutant, the expression of yid) was positively regulated by (p)ppGpp. The growth defect, reduced cell size, and altered fatty acid profile of the Delta fabH mutant and the growth defect of the Delta fabH Delta fabF fabB15(Ts) mutant in oleate- and palmitate-supplemented medium at 42 degrees C were rescued by the expression of yiiD from a multicopy plasmid. Together, these results indicate that the yiiD-encoded function supported initiation of fatty acid biosynthesis in the absence of FabH. We have renamed yiiD as fabY. IMPORTANCE Fatty acid biosynthesis is an essential process conserved across life forms. beta-Ketoacyl-ACP synthases are essential for fatty acid biosynthesis. FabH is a beta-ketoacyl-ACP synthase that contributes to the initiation of fatty acid biosynthesis in Escherichia coli. In this study, we present genetic and biochemical evidence that the yiiD (renamed fabY)-encoded function contributes to the biosynthesis of fatty acid in the absence of FabH activity and that under these conditions, the expression of FabY was regulated by the stringent response factors (p)ppGpp and DksA. Combined inactivation of FabH and FabY resulted in growth arrest, possibly due to the loss of fatty acid biosynthesis. A molecule(s) that inhibits the two activities can be an effective microbicide.