tailieunhanh - Báo cáo khoa học: Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis of phthiocerol dimycocerosates and related compounds in Mycobacterium tuberculosis

Phthiocerol and phthiodiolone dimycocerosates (DIMs) and phenolic gly-colipids (PGLs) are complex lipids located at the cell surface ofMycobacte-rium tuberculosis that play a key role in the pathogenicity of tuberculosis. Most of the genes involved in the biosynthesis of these compounds are clustered on a region of the M. tuberculosischromosome, the so-called DIM + PGL locus. | ỊFEBS Journal Delineation of the roles of FadD22 FadD26 and FadD29 in the biosynthesis of phthiocerol dimycocerosates and related compounds in Mycobacterium tuberculosis Roxane Siméone1 Mathieu Léger1 2 Patricia Constant1 2 Wladimir Malaga1 2 Hedia Marrakchi1 2 Mamadou Daffe1 2 Christophe Guilhot1 2 and Christian Chalut1 2 1 CNRS IPBS Institut de Pharmacologie et de Biologie Structurale Toulouse France 2 Universite de Toulouse UPS IPBS France Keywords fatty acyl-AMP ligase lipid biosynthesis Mycobacterium tuberculosis phenolic glycolipids phthioceroldimycocerosates Correspondence C. Chalut Institut de Pharmacologie et de Biologie Structurale 205 route de Narbonne 31077 Toulouse Cedex France Fax 33 5 61175994 Tel 33 5 61175473 E-mail Present address Unite de Pathogenomique Mycobacterienne Integree Institut Pasteur Paris Cedex France Received 8 March 2010 revised 13 April 2010 accepted 16 April 2010 doi Phthiocerol and phthiodiolone dimycocerosates DIMs and phenolic glycolipids PGLs are complex lipids located at the cell surface of Mycobacterium tuberculosis that play a key role in the pathogenicity of tuberculosis. Most of the genes involved in the biosynthesis of these compounds are clustered on a region of the M. tuberculosis chromosome the so-called DIM PGL locus. Among these genes four ORFs encode FadD proteins which activate and transfer biosynthetic intermediates onto various polyketide synthases that catalyze the formation of these lipids. In this study we investigated the roles of FadD22 FadD26 and FadD29 in the biosynthesis of DIMs and related compounds. Biochemical characterization of the lipids produced by a spontaneous Mycobacterium bovis BCG mutant harboring a large deletion within fadD26 revealed that FadD26 is required for the production of DIMs but not of PGLs. Additionally using allelic exchange recombination we generated an unmarked M. tuberculosis mutant containing a deletion within fadD29.

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