Amphiphilic Cytosolic Glycans from Mycobacteria: Occurrence, Lipid‐Binding Properties, Biosynthesis, and Synthesis

Abstract

Polymethylated polysaccharides (PMPSs), glycans composed of 10-20 carbohydrate residues the majority of which carry a single methyl group, are produced by some mycobacterial species. O-Methylation thus occurs on 20-30% of all the hydroxyl groups within the molecule, rendering them amphiphilic. A property of PMPSs is their ability to form high-affinity complexes with fatty acids and their derivatives, suggesting a role in mycobacterial fatty acid biosynthesis. However, direct evidence for their in vivo function is still lacking. Over the past several decades the lipid-binding properties, biosynthesis, and chemical synthesis of PMPSs have been explored and this review will provide an overview of progress made in these areas.

Biosynthesis of mycobacterial methylmannose polysaccharides requires a unique 1- O -methyltransferase specific for 3- O -methylated mannosides

“…A cluster of genes (Fig. 1B) containing a mannosyltransferase, two putative methyltransferases, and a protein of unknown function, was identified and proposed to coordinate MMP biosynthesis (19,20). Although MTase genes are abundant in mycobacterial genomes, and several glycoconjugates with important structural and functional roles are known to be methylated to a variable extent, the corresponding enzymes, including those required for MGLP and MMP biosynthesis, await characterization.…”

“…Two different mechanisms for MMP biosynthesis have been proposed, one anticipating MMP elongation with alternating mannosylation and methylation reactions (18) and the other arguing for the elongation of an α-1,4-mannosyltransferase (ManT) by several residues followed by methylation by a 3-Omethyltransferase (OMT) (19). Elongation by ManT has been proposed to occur through transfer of mannose from GDPmannose to the O-4 position of a terminal mannose in the growing chain (18)(19)(20) and S-adenosyl-L-methionine (SAM)dependent methylation by OMT taking place at the O-3 position of the mannose units (18).…”

Structure and Stability of Carbohydrate–Lipid Interactions. Methylmannose Polysaccharide–Fatty Acid Complexes

“…The interior of the helix is hydrophobic, and the cavity can accommodate saturated and unsaturated FAs . Other polysaccharides can also form high‐affinity lipid complexes, for example the polymethylated polysaccharides (PMPs) produced by some mycobacteria . There are two classes of PMPs, and they are suggested to play roles in regulating lipid metabolism .…”

“…[22,27,28] Other polysaccharides can also form high-affinity lipid complexes, for example the polymethylated polysaccharides (PMPs) produced by somem ycobacteria. [29] There are two classes of PMPs, and they are suggested to play roles in regulating lipid metabolism. [29,30] One type consists of a-(1!4)-linked 6-O-methyl-Glcp residues (the same anomeric linkages as in amylose) and are assumed to be helical.…”

“…[29] There are two classes of PMPs, and they are suggested to play roles in regulating lipid metabolism. [29,30] One type consists of a-(1!4)-linked 6-O-methyl-Glcp residues (the same anomeric linkages as in amylose) and are assumed to be helical. [31] The other are 3-O-methylmannose polysaccharides (MMPs), which contain a-(1!4)-linked mannopyranose (Manp)m oieties.…”