decaprenylphosphorylDarabinose

Decaprenylphosphoryl compounds refer to lipid-linked sugar donors that participate in bacterial cell wall biosynthesis, most notably in mycobacteria. The best known members are decaprenylphosphoryl-D-ribose (DPR) and its epimer decaprenylphosphoryl-D-arabinose (DPA). The decaprenyl group is a long isoprenoid chain, about C50 in length, anchored in the inner membrane by the phosphate head, which carries the sugar moiety.

In Mycobacterium species, DPR serves as a precursor for arabinan biosynthesis, a critical component of arabinogalactan and lipoarabinomannan in the cell envelope. The conversion of DPR to DPA is catalyzed by the enzyme pair DprE1 and DprE2, which perform oxidation and epimerization to generate the arabinose donor. Arabinosyltransferases then transfer arabinofuranosyl residues from DPA to growing polysaccharide chains, constructing the arabinan portions of arabinogalactan and LAM. This pathway is essential for cell wall integrity and viability in many mycobacteria.

Because the DPR/DPA pathway is vital for cell envelope assembly, it is a target for antimicrobial development. Inhibitors of DprE1, such as benzothiazinones (for example BTZ043), block DPA formation and disrupt cell wall synthesis, demonstrating potent antitubercular activity in research settings.

Decaprenylphosphoryl substrates are studied primarily in the context of mycobacterial biology, where they play a central role in exporting and decorating cell wall glycans. Their function as lipid carriers contrasts with other well-known carriers and highlights unique aspects of mycobacterial cell envelope biogenesis.