Figure 1. Biosynthesis of lipid A in wild-type E. coli K-12.
The first three enzymes are cytoplasmic, whereas the others are peripheral or integral inner membrane proteins that face the cytoplasm (2, 3). LpxL is stimulated ~1000 fold in vitro by the presence of the Kdo disaccharide in its substrate, but its residual activity with lipid IVA is significant (38). The Kdo dependency of LpxM has not been studied in vitro. Mutants of E. coli or Salmonella defective in Kdo biosynthesis or transfer accumulate mainly tetra-acylated lipid IVA and some of its modified derivatives (not shown) (11, 12). No free hexa-acylated lipid A accumulates in Kdo-deficient mutants of cells grown at 30 °C or above.