TABLE 2.

Genetic analysis of the anabolic pathway of mycolic acids in M. tuberculosis and growth requirements

System or groupGeneSanger identificationEnzymeGrowth attenuationcReference(s)
In vitroIn vivo
FAS-IfasRv2524cFatty acid synthetase-IYesd23
FAS-I→FAS-IIfabDRv2243Malonyl-CoA:ACP transacylaseNo51
acpMRv2244Acyl carrier proteinYesNo51
fabHRv0533cβ-Ketoacyl-ACP synthase IIINoNo20, 90
FAS-IIkasA/kasBRv2245/Rv2246β-Ketoacyl-ACP synthaseYes/Yes—/—91
fabG1Rv1483β-Ketoacyl-ACP reductaseNoNo61
Rv0098β-Hydroxyacyl-ACP dehydraseaNoYes25, 71
echA10/echA11Rv1142c/Rv1141c2-trans-Enoyl-ACP isomeraseaNo/NoNo/No60
inhARv14842-trans-Enoyl-ACP reductaseNoNo59
MethyltransferasesmmaA1Rv0645cMmaA1NoNo122, 123
mmaA2Rv0644cMmaA2NoNo41
mmaA3Rv0643cMmaA3NoYes31, 123
mmaA4Rv0642cMmaA4No31, 123
cmaA2Rv0503cCmaA2NoNo39, 42
pcaARv0470cPcaANoYes41
Oxidation-reductionRv0161Alcohol dehydrogenasebNo
Rv0162cNoNo
Rv3057cNoNo
Claisen-type condensationaccD4Rv3799cAcyl-CoA carboxylaseYes23
accD5Rv3280Acyl-CoA carboxylase
fadD32Rv3801cFatty acyl-AMP ligaseYes107
pks13Rv3800cPolyketide synthase-13Yes76
Mycolic acid processingRv3802cMycolyltransferases IbYes
Rv1288/Rv0519c/Rv0774cMycolyltransferases IIbNo/NoNo/No
Rv0774cNoNo
Rv3400TMM-6-P phosphatasebNoYes
Rv2006NoNo
Rv1273c/Rv1272cABC transporterbNo/NoNo/Yes17
Rv1348/Rv1349Yes/Yes—/—
Rv0194NoNo
Rv1819cNoNo
Rv1747NoNo
Rv1687c/Rv1686cNo/NoNo/No
fbpA/fbpB/fbpCRv3804c/Rv1886c/Rv0129cFbpA/FbpB/FbpCNo/No—/No4, 45, 77
NoNo
  • a Dehydrase and isomerase are thought to be in the pathway to meroacid synthesis, but they have not been identified. We suggest possible genes that encode the two enzymes.

  • b The enzyme is hypothetical. We have identified possible gene and gene products involved in these proposed reactions (Fig. 8).

  • c The in vitro growth rate was determined by microarray analysis of an M. tuberculosis strain H37Rv transposon mutant library grown on agar plates (87). The in vivo growth rate was determined by microarray analysis of surviving bacteria in C57BL/6J mice infected with an M. tuberculosis strain H37Rv transposon mutant library (88).

  • d —, gene was not detected reproducibly.