%0 Figure %A Alahari, Anuradha %A Trivelli, Xavier %A Guérardel, Yann %A G. Dover, Lynn %A Besra, Gurdyal S. %A Sacchettini, James C. %A Reynolds, Robert C. %A Coxon, Geoffrey D. %A Kremer, Laurent %D 2013 %T Proposed mechanism for generation of mycolic acid sub-types by the action of CMAS enzymes (A) and inhibition by TAC/SRI-224 (B). %U https://plos.figshare.com/articles/figure/_Proposed_mechanism_for_generation_of_mycolic_acid_sub_types_by_the_action_of_CMAS_enzymes_A_and_inhibition_by_TAC_SRI_224_B_/611393 %R 10.1371/journal.pone.0001343.g008 %2 https://ndownloader.figshare.com/files/940976 %K mycolic %K sub-types %K cmas %K enzymes %K inhibition %X

The generation of α- and the oxygenated mycolic acids is considered to follow to two independent pathways. A common, di-unsaturated precursor, Y, is envisaged for the two pathways. Y is subsequently transformed into α-mycolic acids by the action of the MmaA2 and PcaA that modify the distal or proximal double bond, respectively. Action of MmaA4 commits Y to the pathway for the oxygenated mycolic acids, by producing the precursor X. MmaA3, which is required for generation of methoxy-mycolic acids in M. tb is inactive in M. bovis BCG Pasteur due to the presence of a point mutation [50]. The proximal double bond is modified by the CmaA2 (and MmaA2) or PcaA to generate trans- or cis-cyclopropanated derivatives, respectively. In the presence of TAC, all the CMASs mentioned above are inhibited, except for MmaA4. Due to inhibition of MmaA2, excess of Y is diverted to MmaA4 leading to generation of X, which accumulates due to lack of activities of CmaA2 and MmaA2. SRI-224 appears to affect MmaA4 to a certain degree, leading to accumulation Y in addition to X. (For simplicity, only the meromycolyl moiety of mycolates has been depicted).

%I PLOS ONE