Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis of phthiocerol dimycocerosates and related compounds in Mycobacterium tuberculosis

摘要: Phthiocerol and phthiodiolone dimycocerosates (DIMs) phenolic glycolipids (PGLs) are complex lipids located at the cell surface of Mycobacterium tuberculosis that play a key role in pathogenicity tuberculosis. Most genes involved biosynthesis these compounds clustered on region M. chromosome, so-called DIM + PGL locus. Among genes, four ORFs encode FadD proteins, which activate transfer biosynthetic intermediates onto various polyketide synthases catalyze formation lipids. In this study, we investigated roles FadD22, FadD26 FadD29 DIMs related compounds. Biochemical characterization produced by spontaneous bovis BCG mutant harboring large deletion within fadD26 revealed is required for production but not PGLs. Additionally, using allelic exchange recombination, generated an unmarked containing fadD29. analyses strain that, like fadD22, gene encodes protein specifically PGLs, indicating both FadD22 responsible one particular reaction pathway. These findings were also supported vitro enzymatic studies showing enzymes have different properties, displaying p-hydroxybenzoyl-AMP ligase activity, fatty acyl-AMP activity. Altogether, data allowed us to precisely define functions fulfilled proteins encoded cluster.