The dual function of the Mycobacterium tuberculosis FadD32 required for mycolic acid biosynthesis.
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Leger M, Gavalda S, Guillet V, van der Rest B, Slama N, Montrozier H, Mourey L, Quemard A, Daffe M, Marrakchi H
The dual function of the Mycobacterium tuberculosis FadD32 required for mycolic acid biosynthesis.
Chem Biol. 2009 May 29;16(5):510-9. doi: 10.1016/j.chembiol.2009.03.012.
- PubMed ID
- 19477415 [ View in PubMed]
- Abstract
Mycolic acids are major and specific lipids of Mycobacterium tuberculosis cell envelope. Their synthesis requires the condensation by Pks13 of a C(22)-C(26) fatty acid with the C(50)-C(60) meromycolic acid activated by FadD32, a fatty acyl-AMP ligase essential for mycobacterial growth. A combination of biochemical and enzymatic approaches demonstrated that FadD32 exhibits substrate specificity for relatively long-chain fatty acids. More importantly, FadD32 catalyzes the transfer of the synthesized acyl-adenylate onto specific thioester acceptors, thus revealing the protein acyl-ACP ligase function. Therefore, FadD32 might be the prototype of a group of M. tuberculosis polyketide-synthase-associated adenylation enzymes possessing such activity. A substrate analog of FadD32 inhibited not only the enzyme activity but also mycolic acid synthesis and mycobacterial growth, opening an avenue for the development of novel antimycobacterial agents.