Chemical Insight into the Mechanism and Specificity of GlfT2, a Bifunctional Galactofuranosyltransferase from Mycobacteria

Mycobacteria, including the human pathogen Mycobacterium tuberculosis, produce a complex cell wall structure that is essential to survival. A key component of this structure is a glycoconjugate, the mycolyl-arabinogalactan-peptidoglycan complex, which has at its core a galactan domain composed of galactofuranose (Galf) residues linked to peptidoglycan. Because galactan biosynthesis is essential for mycobacterial viability, compounds that interfere with this process are potential therapeutic agents for treating mycobacterial diseases, including tuberculosis. Galactan biosynthesis in mycobacteria involves two glycosyltransferases, GlfT1 and GlfT2, which have been the subject of increasing interest in recent years. This Synopsis summarizes efforts to characterize the mechanism and specificity of GlfT2, which is responsible for introducing the majority of the Galf residues into mycobacterial galactan.