The ability of bacteria to control the biophysical properties of their membrane phospholipids allows them to thrive in a wide range of physical environments. Bacteria precisely adjust their membrane lipid composition by modifying the types of fatty acids that are produced by the biosynthetic pathway and altering the structures of pre-existing phospholipids. The recycling of phospholipids that are used as intermediates in the biosynthesis of other major membrane components is also crucial to bilayer stability in dividing cells. Here, the principal genetic and biochemical processes that are responsible for membrane lipid homeostasis in bacteria are reviewed.

The type II fatty acid synthetic pathway is the principal route for the production of membrane phospholipid acyl chains in bacteria and plants. The reaction sequence is carried out by a series of individual soluble proteins that are each encoded by a discrete gene, and the pathway intermediates are shuttled between the enzymes as thioesters of an acyl carrier protein. The Escherichia coli system is the paradigm for the study of this system, and high-resolution X-ray and/or NMR structures of representative members of every enzyme in the type II pathway are now available. The structural biology of these proteins reveals the specific three-dimensional features of the enzymes that explain substrate recognition, chain length specificity, and the catalytic mechanisms that define their roles in producing the multitude of products generated by the type II system. These structures are also a valuable resource to guide antibacterial drug discovery.

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H333N] was significantly more resistant to both antibiotics than FabB and had an affinity for TLM an order of magnitude less than the wild-type enzyme, illustrating that the two-histidine active site architecture is critical to protein-antibiotic interaction. These data provide a structural framework for understanding antibiotic sensitivity within this group of enzymes.