TABLE 2.

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

System or group	Gene	Sanger identification	Enzyme	Growth attenuationc		Reference(s)
				In vitro	In vivo
FAS-I	fas	Rv2524c	Fatty acid synthetase-I	Yes	—d	23
FAS-I→FAS-II	fabD	Rv2243	Malonyl-CoA:ACP transacylase	—	No	51
	acpM	Rv2244	Acyl carrier protein	Yes	No	51
	fabH	Rv0533c	β-Ketoacyl-ACP synthase III	No	No	20, 90
FAS-II	kasA/kasB	Rv2245/Rv2246	β-Ketoacyl-ACP synthase	Yes/Yes	—/—	91
	fabG1	Rv1483	β-Ketoacyl-ACP reductase	No	No	61
		Rv0098	β-Hydroxyacyl-ACP dehydrasea	No	Yes	25, 71
	echA10/echA11	Rv1142c/Rv1141c	2-trans-Enoyl-ACP isomerasea	No/No	No/No	60
	inhA	Rv1484	2-trans-Enoyl-ACP reductase	No	No	59
Methyltransferases	mmaA1	Rv0645c	MmaA1	No	No	122, 123
	mmaA2	Rv0644c	MmaA2	No	No	41
	mmaA3	Rv0643c	MmaA3	No	Yes	31, 123
	mmaA4	Rv0642c	MmaA4	No	—	31, 123
	cmaA2	Rv0503c	CmaA2	No	No	39, 42
	pcaA	Rv0470c	PcaA	No	Yes	41
Oxidation-reduction		Rv0161	Alcohol dehydrogenaseb	—	No
		Rv0162c		No	No
		Rv3057c		No	No
Claisen-type condensation	accD4	Rv3799c	Acyl-CoA carboxylase	Yes	—	23
	accD5	Rv3280	Acyl-CoA carboxylase	—	—
	fadD32	Rv3801c	Fatty acyl-AMP ligase	Yes	—	107
	pks13	Rv3800c	Polyketide synthase-13	Yes	—	76
Mycolic acid processing		Rv3802c	Mycolyltransferases Ib	Yes	—
		Rv1288/Rv0519c/Rv0774c	Mycolyltransferases IIb	No/No	No/No
		Rv0774c		No	No
		Rv3400	TMM-6-P phosphataseb	No	Yes
		Rv2006		No	No
		Rv1273c/Rv1272c	ABC transporterb	No/No	No/Yes	17
		Rv1348/Rv1349		Yes/Yes	—/—
		Rv0194		No	No
		Rv1819c		No	No
		Rv1747		No	No
		Rv1687c/Rv1686c		No/No	No/No
	fbpA/fbpB/fbpC	Rv3804c/Rv1886c/Rv0129c	FbpA/FbpB/FbpC	No/No	—/No	4, 45, 77
				No	No

^aDehydrase 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.

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

^cThe 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.