Caister Academic Press

Novel paradigms of complex lipid biosynthetic machinery of Mycobacterium tuberculosis

Arush Chhabra and Rajesh S. Gokhale
from: Mycobacterium: Genomics and Molecular Biology (Edited by: Tanya Parish and Amanda Brown). Caister Academic Press, U.K. (2009)

Abstract

Mycobacterium tuberculosis posseses a repertoire of complex lipids. Many of these lipids are crucial to its survival and virulence. Fatty-acyl components of the mycobacterial lipids are synthesised by the concerted action of fatty acid synthases (FASs) and polyketide synthases (PKSs). While the single multifunctional type I FAS carries out de novo biosynthesis from acetyl-CoA, the multicomponent type II FAS generates the very long acyl chains from type I FAS products. Polyketide synthases take over from FAS to complete the biosynthesis of the unusual acyl chains of many exotic lipids like mycolic acids, phthioceroldimycocerosate ester, sulfolipids and mannosyl-beta-1-phophomycoketides. The novel family of fatty acyl-adenylate ligases (FAALs) is crucial to this intricate enzymatic network. FAALs mediate the crosstalk between FAS and PKS by activating long-chain fatty acids to fatty acyl-adenylates which are transacylated onto the PKSs. In this chapter we describe novel components of lipid biosynthetic network, several of which could prove to be promising drug targets read more ...
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