Membrane lipid homeostasis is a vital facet of bacterial cell physiology. For decades, research in bacterial lipid synthesis was largely confined to the Escherichia coli model system. This basic research provided a blueprint for the biochemistry of lipid metabolism that has largely defined the individual steps in bacterial fatty acid and phospholipids synthesis. The advent of genomic sequencing has revealed a surprising amount of diversity in the genes, enzymes and genetic organization of the components responsible for bacterial lipid synthesis. Although the chemical steps in fatty acid synthesis are largely conserved in bacteria, there are surprising differences in the structure and cofactor requirements for the enzymes that perform these reactions in Gram-positive and Gram-negative bacteria. This review summarizes how the explosion of new information on the diversity of biochemical and genetic regulatory mechanisms has impacted our understanding of bacterial lipid homeostasis. The potential and problems of developing therapeutics that block pathogen phospholipid synthesis are explored and evaluated. The study of bacterial lipid metabolism continues to be a rich source for new biochemistry that underlies the variety and adaptability of bacterial life styles.
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