Transcription of the Escherichia coli Fatty Acid Synthesis Operon fabHDG Is Directly Activated by FadR and Inhibited by ppGpp

In Escherichia coli, FadR and FabR are transcriptional regulators that control the expression of fatty acid degradation and unsat-urated fatty acid synthesis genes, depending on the availability of fatty acids. In this report, we focus on the dual transcriptional regulator FadR. In the absence of fatty acids, FadR represses the transcription of fad genes required for fatty acid degradation. However, FadR is also an activator, stimulating transcription of the products of the fabA and fabB genes responsible for unsatu-rated fatty acid synthesis. In this study, we show that FadR directly activates another fatty acid synthesis promoter, PfabH, which transcribes the fabHDG operon, indicating that FadR is a global regulator of both fatty acid degradation and fatty acid synthesis. We also demonstrate that ppGpp and its cofactor DksA, known primarily for their role in regulation of the synthesis of the translational machinery, directly inhibit transcription from the fabH promoter. ppGpp also inhibits the fadR promoter, thereby reducing transcription activation of fabH by FadR indirectly. Our study shows that both ppGpp and FadR have direct roles in the control of fatty acid promoters, linking expression in response to both translation activity and fatty acid availability. The biochemical pathways for fatty acid and phospholipid syn-thesis and for fatty acid degradation have been studied exten-sively in bacteria, especially in Escherichia coli (1–3). Type II fatty acid synthesis (FASII) takes place in the cytoplasm, and enzymes have been identified that account for each step in the pathway. In this pathway, acyl carrier protein (ACP) acts as a cofactor by shut