Mycocerosic acids

The mycobacterial cell wall, discussed in Chapter 8, contains mycolic acids bound covalently at the nonreducing ends of arabinogalac-tans that are attached to the inner peptidoglycan layer,e as well as phosphatidylinositol-anchored lipoarabinomannans. Other unusual lipids that are also present and account for some of the difficulty of treatment with antibiotics include esters of mycocerosic acid with long-chain diols known as phenolphthiocerols and phthiocerols.f/fg... 

Information on the biosynthesis of the phenolic glycolipids is very limited.220 The carbon atoms in the methyl-branched structures in mycocerosic acids are derived from propanoate.221-222 So also are those in phthiocerol.223 224 The aromatic ring can be derived from tyrosine.224 The methoxyl residue in phenolphthiocerol presumably comes from methionine, by analogy with the known source in the related lipid phthiocerol.225 226 Rainwater and Kolatukuddy226 demonstrated two steps in the biosynthesis of mycocerosic acids, and isolated the enzymes involved, but the biosynthetic steps leading to phenolphthiocerol itself are not known. 

The lipid moiety of the glycolipids under consideration is either composed of branched-chain fatty acids (for example, mycolic acids in cord factor and in wax D) or can be a wax formed by the union of a phenolic alcohol with branched-chain fatty acids of the mycocerosic acid type, as in mycosides A and B. In the phosphoglycolipids, simple normal fatty acids have been found, accompanied by some methyl branched acids. 

B. ter Horst, B. L. Feringa, A. J. Miimaard, Catalytic asymmetric synthesis of mycocerosic acid, Chem. Commun., 2007, 489-491. 

Complex waxes are compounds where either the fatty acid or the alcohol component or both has a complex structure. For example, the waxes of Mycobacterium spp. are diesters of phthiocerols (C33-C35 branched-chain diols) with mycocerosic acids (C29-C32 branched-chain acids) (Asselineau, 1966). 

Constit. of Mycocerosic acid, a laevorotatory acid obt. from the lipids of tubercle bacilli. 

Monoolein, in G-00207 a-Monoolein, in G-00206 /8-Monoolein, in G-00207 a-Monopalmitin, see G-OOl 34 /8-Monopalmitin, see G-OOl 35 a-Monostearin, see G-OOl75 /8-Monostearin, see G-OOl76 Montanic acid, see 0-00009 Montanol, M-OOl31 Montanyl alcohol, see 0-00010 Muscalure, in T-00126 Mycoceranic acid, see T-00207 Mycocerosic acid, see T-00207... 

The common carbon sequence in all these molecules has the (CH2CHCH3CH2CH2) architecture. Mycocerosic acid has the formula C32H64O2 (2,4,6,8-tetramethyloctacosanoic acid) and has four branches in the principal chain. Branched fatty acids (the mycolic acids) are found in bacteria belonging to the Mycobacterium-Nocardia-Corynebacterium group. They have often other functional groups in their chain, and should formally belong to the multifunctional fatty acids. 

Structural considerations suggest a close biosynthetic relationship between these non-isoprenoid methyl-branched metabolites. Two possible origins can be considered for the methyl groups (i) from methionine as in the monomethylalkanes synthesized by blue-green algae 63) (ii) from insertion of methylmalonate instead of malonate during the elongation process, as in the multiple-branched mycocerosic acids produced by mycobacteria (64). 

Li, M.-S., Monahan, I.M., Waddell, S.f. et al. (2001) cDNA-RNA subtractive hybridisation reveals increased expression of mycocerosic acid synthase in intracellular Mycobacterium bovis BCG. Microbiology, 147, 2293-2305. 

Figure 6.17 Some mycobacterial lipids. Structures of mycobacterial lipids (a) trehalose mycolate. where Ri and R2 are mycollc acids (b) suiphoiipid. where R1-R4 are palmitic acid or very long chain branched fatty acids (c) mycosides A and B. where R is a mono- or trisaccharide and R2 is a 12-18C saturated fatty acid or a mycocerosic acid (e.g. CH3(CH2)2i(CH(CH3)CH2)2CH(CH3)COOH).

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