The Methyl-Branched Fortifications of Mycobacterium tuberculosis

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The Methyl-Branched Fortifications of Mycobacterium tuberculosis David E Minnikin, Laurent Kremer, Lynn G Dover, Gurdyal S Besra Chemistry & Biology Volume 9, Issue 5, Pages 545-553 (May 2002) DOI: 10.1016/S1074-5521(02)00142-4

Figure 1 Structures of M. tuberculosis Mycolic Acids and Glycolipids, Based on Trehalose (A) Schematic representation of the α, methoxy-, and ketomycolic acids from M. tuberculosis. (B) Trehalose dimycolate (TDM) from M. tuberculosis. (C) Complex glycolipids from M. tuberculosis. Sulfated tetra-acyl trehalose (SL1) based on phthioceranic and hydroxyphthioceranic acids, diacyl trehaloses (DAT1) based on mycosanoic acids, triacyl trehalose (TAT) and pentaacyl trehalose (PAT) based on mycolipenic acids. Chemistry & Biology 2002 9, 545-553DOI: (10.1016/S1074-5521(02)00142-4)

Figure 2 Structures of M. tuberculosis Complex Mycoside B, Phthiocerol Dimycocerosate, and Related Genomics (A) Mycoside B (PGL) from M. bovis BCG. (B) Phthiocerol dimycocerosate A (PDIM A) from M. tuberculosis. (C) The genomic organization of surrounding open reading frames that produce and transport PGL/PDIM. Chemistry & Biology 2002 9, 545-553DOI: (10.1016/S1074-5521(02)00142-4)

Figure 3 Arrangement of Structural Components in the Cell Envelope of M. tuberculosis, Showing Possible Interaction of Methyl-Branched Long-Chain Components with a Mycolic Acid Matrix Mycolyl arabinogalactan (mAG) is connected by a phosphoryl linker unit to peptidoglycan (PG). Complex free lipids (PDIM, DAT, PAT, SL; see Figures 1 and 2) interact with mAG. Lipoarabinomannan (LAM) and phosphatidylinositol pentamannoside (PIM5) are shown anchored in the plasma membrane. The mAG galactan is shown in yellow, and the LAM mannose components are in dark green; the arabinan of both these polysaccharides is represented in light blue. Modified from references [7] and [22]. The figure is principally designed to indicate the possible location and interactions of the methyl-branched components; the outermost carbohydrate/protein-rich layer [23] is omitted for clarity. Chemistry & Biology 2002 9, 545-553DOI: (10.1016/S1074-5521(02)00142-4)

Figure 4 Structures of and Proposed Biosynthetic Pathways Leading to the Complex Multimethyl-Branched Fatty Acids from M. tuberculosis See text for abbreviations. Chemistry & Biology 2002 9, 545-553DOI: (10.1016/S1074-5521(02)00142-4)

Figure 5 Structures of Phthiocerol and Phenolphthiocerol Families from the M. tuberculosis Complex and Proposed Pathways Leading to Their Biosynthesis Adapted from Azad et al. [54]. See text for abbreviations. Chemistry & Biology 2002 9, 545-553DOI: (10.1016/S1074-5521(02)00142-4)

Figure 6 Domain Organization among pks Families from M. tuberculosis (A) Known pks genes (B) Unknown pks genes The domain organization consists of the subunits β-ketoacyl synthase (KS), acyl transferase (AT), dehydratase (DH), enoyl reductase (ER), β-ketoreductase (KR), acyl carrier protein (ACP), thioesterase (TE), and chalcone synthase-like (CHS?). Chemistry & Biology 2002 9, 545-553DOI: (10.1016/S1074-5521(02)00142-4)