TABLE 1.

Assembly line array models of mycolate synthetases in M. tuberculosis

EnzymeAssembly line array modela
α-Mycolate synthetaseFAS-I→FAS-IIA→[FAS-II]5→FAS-IIB→[FAS-II]8→MeTnfb→[Pks13][FAS-I]
cis-Methoxy-mycolate synthetaseFAS-I→FAS-IIA→[FAS-II]8→FAS-IIB→[FAS-II]8→MmaA4/MeTnf→[Pks13][FAS-I]
trans-Methoxy-mycolate synthetaseFAS-I→FAS-IIA→[FAS-II]8→FAS-IIB→[FAS-II]8→MmaA4/MmaA1/MeTnf→[Pks13][FAS-I]
cis-Keto-mycolate synthetaseFAS-I→FAS-IIA→[FAS-II]8→FAS-IIB→[FAS-II]9→MmaA4/Redox/MeTnf→[Pks13][FAS-I]
trans-Keto-mycolate synthetaseFAS-I→FAS-IIA→[FAS-II]8→FAS-IIB→[FAS-II]9→MmaA4/MmaA1/Redox/MeTnf→ [Pks13][FAS-I]
  • a The three different FAS-II modules are FAS-II (see Fig. 3 for composition) for elongation, FAS-IIA (containing FabD, β-hydroxyacyl-ACP synthase-III, β-ketoacyl- ACP reductase, β-hydroxyacyl-ACP dehydrase, and 2-trans-enoyl-ACP isomerase) for introduction of distal cis unsaturation, and FAS-IIB (containing FabD, β-ketoacyl-ACP synthase, β-ketoacyl-ACP reductase, β-hydroxyacyl-ACP dehydrase, and 2-trans-enoyl-ACP isomerase) for introduction of proximal cis unsaturation. These reactions and enzymes are shown in Fig. 4. MmaA4 introduces the distal-branch methyl and adjacent hydroxyl groups. MmaA1 introduces the proximal allylic methyl branch and trans unsaturation. Redox converts the distal secondary alcohol to the oxo group. FAS-I provides eicosanoyl-S-CoA at the beginning with FAS-IIA and hexacosanoyl-S-CoA for the final condensation reaction with Pks13.

  • b MeTnf, methyltransferases (including cyclopropane synthase).