Structural basis of phosphatidyl-myo-inositol mannosides biosynthesis in mycobacteria

Phosphatidyl-myo-inositol mannosides (PIMs) are glycolipids of unique chemical structure found in the inner and outer membranes of the cell envelope of all Mycobacterium species. The PIM family of glycolipids comprises phosphatidyl-myo-inositol mono-, di-, tri-, tetra-, penta-, and hexamannosides with different degrees of acylation. PIMs are considered not only essential structural components of the cell envelope but also the precursors of lipomannan and lipoarabinomannan, two major lipoglycans implicated in host-pathogen interactions. Since the description of the complete chemical structure of PIMs, major efforts have been committed to defining the molecular bases of its biosynthetic pathway. The structural characterization of the integral membrane phosphatidyl-myo-inositol phosphate synthase (PIPS), and that of three enzymes working at the protein-membrane interface, the phosphatidyl-myo-inositol mannosyltransferases A and B, and the acyltransferase PatA, established the basis of the early steps of the PIM pathway at the molecular level. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop.