Fig 5. Hypothesis of possible mechanistic bases of distinct fatty acid composition of free lipid A vs. lipid A linked to the HMW O-Ag capsule in F. tularensis.
Lipid IVA contains 4 mol of 3-OH fatty acid per mol of lipid A (3-OH-18:0 >>3-OH-16:0). LpxL1/2 are homologous "late" acyltransferases that subsequently incorporate the single non-hydroxylated fatty acid of F. tularensis lipid A. Based in part on Raetz et al., we hypothesize that only one (arbitrarily, in this figure, LpxL1) is KDO-dependent and selective for C14:0 whereas LpxL2 is KDO-independent and selective for 16:0 [25]. The different 3-OH-FA composition of free lipid A and lipid linked to HMW O-Ag capsule could reflect the substrate specificity of KdtA that incorporates KDO into lipid IVA.