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-I fas Rv2524c Fatty acid synthetase-IYesd 23
FAS-I→FAS-II fabD Rv2243 Malonyl-CoA:ACP transacylaseNo 51
acpM Rv2244 Acyl carrier proteinYesNo 51
fabH Rv0533c β-Ketoacyl-ACP synthase IIINoNo 20, 90
FAS-II kasA/kasB Rv2245/Rv2246 β-Ketoacyl-ACP synthaseYes/Yes—/— 91
fabG1 Rv1483 β-Ketoacyl-ACP reductaseNoNo 61
Rv0098 β-Hydroxyacyl-ACP dehydraseaNoYes 25, 71
echA10/echA11 Rv1142c/Rv1141c 2-trans-Enoyl-ACP isomeraseaNo/NoNo/No 60
inhA Rv1484 2-trans-Enoyl-ACP reductaseNoNo 59
Methyltransferases mmaA1 Rv0645c MmaA1NoNo 122, 123
mmaA2 Rv0644c MmaA2NoNo 41
mmaA3 Rv0643c MmaA3NoYes 31, 123
mmaA4 Rv0642c MmaA4No 31, 123
cmaA2 Rv0503c CmaA2NoNo 39, 42
pcaA Rv0470c PcaANoYes 41
Oxidation-reduction Rv0161 Alcohol dehydrogenasebNo
Rv0162c NoNo
Rv3057c NoNo
Claisen-type condensation accD4 Rv3799c Acyl-CoA carboxylaseYes 23
accD5 Rv3280 Acyl-CoA carboxylase
fadD32 Rv3801c Fatty acyl-AMP ligaseYes 107
pks13 Rv3800c Polyketide synthase-13Yes 76
Mycolic acid processing Rv3802c Mycolyltransferases IbYes
Rv1288/Rv0519c/Rv0774c Mycolyltransferases IIbNo/NoNo/No
Rv0774c NoNo
Rv3400 TMM-6-P phosphatasebNoYes
Rv2006 NoNo
Rv1273c/Rv1272c ABC transporterbNo/NoNo/Yes 17
Rv1348/Rv1349 Yes/Yes—/—
Rv0194 NoNo
Rv1819c NoNo
Rv1747 NoNo
Rv1687c/Rv1686c No/NoNo/No
fbpA/fbpB/fbpC Rv3804c/Rv1886c/Rv0129c FbpA/FbpB/FbpCNo/No—/No 4, 45, 77
  • 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.