The dual function of the Mycobacterium tuberculosis FadD32 required for mycolic acid biosynthesis.

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Citation

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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Medium-chain fatty-acid--CoA ligaseP38135Details