Significance The bacterial envelope is composed of a diverse set of polysaccharides. Virtually all of these polymers are synthesized from lipid-linked precursors that are flipped across the cytoplasmic membrane by ATP-binding cassette transporters or multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) exporter superfamily members. Transport of the cell wall precursor lipid II requires the MOP family member MurJ in Escherichia coli . Here, we provide evidence for a novel lipid II flippase in Bacillus subtilis called alternate to MurJ (Amj), which bears no similarity to either family of transporters. amj is up-regulated in the absence of B. subtilis MurJ (MurJ _Bs ) via an envelope stress-response pathway, suggesting this novel flippase may serve as a defense mechanism against naturally occurring MurJ antagonists.