Polymethylated polysaccharides from Mycobacterium species revisited

Abstract

Mycobacteria produce two sets of unusual polymethylated polysaccharides, the 3-O-methylmannose polysaccharides and the 6-O-methylglucose lipopolysaccharides. Both polysaccharides localize to the cytoplasm, where they have been postulated to regulate fatty acid metabolism due to their ability to form stable 1:1 complexes with fatty acyl chains. Physiological evidence for this assumption is lacking, however. Recent advances in our knowledge of the processes underlying sugar transfer in mycobacteria, together with the availability of genome sequences and tools for the genetic manipulation of these microorganisms, have opened the way to the elucidation of the biosynthetic pathways and biological functions of these unique carbohydrates.

FIGURE 1.

Structure and genetics of MGLPs and MMPs. A, structures of the MGLPs from M. bovis BCG and MMPs from M. smegmatis (n = 10–13). R1, R2, and R3 are acyl groups: R1, acetate, propionate, or isobutyrate; R2, octanoate; and R3, succinate. B, proposed biosynthetic model of MGLPs (20) with the names of the genes thought to be involved in the different steps of their elongation and modifications now indicated. Acylation and methylation are thought to occur concurrently; the precise stage at which the two β-(1→3)-linked Glc residues are attached is not known, but the definition of early MGLP precursors (20) suggests that they are added early during the elongation process. GpgP is an unknown phosphatase. C, organization and proposed functions of the two gene clusters involved in the biosynthesis of MGLPs in M. tuberculosis H37Rv (see text for details). The genes likely to be involved in MGLP synthesis are in black; genes of unknown function or involved in other pathways are in gray. In M. tuberculosis H37Rv, the start codon of Rv3031 overlaps the stop codon of Rv3030, and Rv3031 and Rv3032 are separated by an intergenic region of 32 bp. Nothing is known of the genetics of MMP synthesis.

FIGURE 2.

A, top and side views of a structural model of MGP containing 19 glucosyl units of which 12 are O-methylated (MGP_19,12); B, structural model of stearic acid (in green) bound to MGP_20,12.