Diverse lipid A structures have been observed in a multitude of Gram-negative bacteria, but the metabolic logic of lipid A biosynthesis is widely conserved. This chapter will start by describing the nine constitutive enzymes of the Raetz pathway, which catalyze conserved lipid A biosynthetic reactions that depend on cytoplasmic cofactors. Concomitant with lipid A export and assembly on the cell surface, a number of regulated covalent modifications of lipid A can occur in the extracytoplasmic compartments. The narrow phylogenetic distribution of the lipid A modification enzymes, combined with the diverse regulatory signals governing their expression, is responsible for most of the lipid A structural diversity that is observed in nature. By focusing on E. coli as a model system, the general principles of lipid A biosynthesis and assembly are revealed to inform related processes that occur in more divergent organisms.
Work in the author’s laboratory was supported by the Canadian Institutes of Health Research. We apologize to those authors whose work could not be cited due to space limitations.
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