Phthiocerol

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... 

A strong case has also been made for the PGL-I and related dimycocerosyl phthiocerol in the intracellular survival of M. leprae. Early investigators of the microscopic properties of M. leprae noted material (capsular matrices, transparent... 

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. 

Another wax fraction ( soft wax ) obtained by Anderson yielded glycerol, an alcohol, and ether-soluble substances on hydrolysis. The alcohol was again phthiocerol, the presence of which was first reported by Stodola and Anderson. ... 

Anderson found that a substance of lipid nature was associated with the skeletal material of acid-fast bacilli. This lipid was not removed by neutral organic solvents but could be extracted with an ethereal or chloroform solution of hydrogen chloride. Saponification of these firmly-bound lipids yielded a polysaccharide having properties similar to those of the polysaccharide obtained from the purified wax. Phthiocerol was not detected. The polysaccharide was shown to contain... 

The distribution of these substances in the various species of Mycobacteria is as follows. (a) Phthiocerol dimycocerosate is present in the lipids of 28 out of 30 human strains studied, (b) A compound first called Gb is present in the lipids of 7 out of 7 bovine strains studied (Gb is accompanied by phthiocerol dimycocerosate in virulent, bovine strains), (c) A compound first called Ga is present in the lipids of 17 out of 17 photochromogenic strains, (d) A compound first called Jav is present in the lipids of 11 out of 13 avian strains, and also in the lipids of 3 out of 6 non-photochromogenic strains. 

Mycobacterium spp. Phenolic glyco- - o>-[(4-Glycosylo5Qr)phenyl]phthiocerol 63 75 Worldwide... 

Some of this group are listed in Table 13.3 All the members are 3-alkenylphenols sometimes, as with campnospermanol, containing a keto function in the side chain. The highly unsaturated substance flexirubin is a phenolic ester from a bacterial source. Complex phenolic ether compounds, essentially 0-glycosyl derivatives of c6-(4-hydroxyphenyl)phthiocerol A have been isolated from mycobacterial sources (ref. 75). 

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). 

Specific polyketide hpids present in M. tuberculosis interact with the host and are required for virulence. Mass spectrometric analysis was conducted to monitor this type of lipids [53]. It was discovered that the size and abundance of two lipid virulence factors, phthiocerol dimycocerosate and sulfolipid-1, were controlled by the availability of a common precursor, methyl malonyl CoA. These results suggested that growth of M. tuberculosis on fatty acids during infection led to increased flux of methyl malonyl CoA through lipid biosynthetic pathways, resulting in increased virulence lipid synthesis. 

The C-4 carbon in phthiocerol A has been assigned the 5-configuration. Acetals and Thioacetals.—A catalytic dehydrator for rapid acetal synthesis has been described a combination of an acid ion-exchange resin and a drying agent is used. Ingenious use is made of molecular sieves in a related... 

Other Long-chain Compounds.— The absolute configuration of phthiocerol A (1 la), phthiotriol A (1 lb), and phthiodolone A (1 Ic) has been established... 

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