FtsW is a peptidoglycan polymerase that is functional only in complex with its cognate penicillin-binding protein

The peptidoglycancell wall is essential for the survival and morphogenesis of bacteria1. For decades, it was thought that only class A penicillin-binding proteins(PBPs) and related enzymes effected peptidoglycan synthesis. Recently, it was shown that RodA—a member of the unrelated SEDS protein family—also acts as a peptidoglycanpolymerase2–4. Not all bacteria require RodA for growth; however, its homologue, FtsW, is a core member of the divisome complex that appears to be universally essential for septal cell wall assembly5,6. FtsW was previously proposed to translocate the peptidoglycanprecursor lipid IIacross the cytoplasmic membrane7,8. Here, we report that purified FtsW polymerizes lipid IIinto peptidoglycan, but show that its polymerase activity requires complex formation with its partner class B PBP. We further demonstrate that the polymerase activity of FtsW is required for its function in vivo. Thus, our findings establish FtsW as a peptidoglycanpolymerase that works with its cognateclass B PBP to produce septal peptidoglycanduring cell division.