Carbohydrate Polymer Biosynthesis: Controlling Length

The biological function of a polysaccharide depends on its length. Unlike nucleic acids and proteins, carbohydrate polymer biosynthesis occurs without a template. For template-independent polymerization reactions, little is known about how length is controlled. To address this issue, we focused on the carbohydrate polymerase GlfT2, which builds the galactofuranose-containing polysaccharide in the cell wall of mycobacteria (including Mycobacterium tuberculosis). We devised a mass spectrometry assay and used it to reveal that GlfT2 is a processive polymerase with an intrinsic ability to control polymer length. Results prompted us to propose a model for polysaccharide length control. The carbohydrate polymerase GlfT2 binds to both ends of the growing polysaccharide. When the polysaccharide gets too long, the enzyme cannot maintain multipoint binding so the complex dissociates. In this way, the length of the polysaccharide depends on the multipoint binding. This mode of tethering is a general strategy that other carbohydrate polymerases could use to regulate polysaccharide length.