Figure 1

Functions of the proteins encoded by the tag and tar genes in the biosynthesis of poly(Gro-P)- and poly(Rbo-P)-containing WTA backbones, respectively [adapted from [9]. Numbers between brackets indicate the gene-identifiers of tag and tar homologues in the L. plantarum WCFS1 genome and Rib represents ribulose. Regardless of the backbone type, the biosynthesis of WTA is initiated with the consecutive coupling of UDP-activated N-acetylglucosamine (GlcN ac) and N-acetylmannosamine (ManN ac) to undecaprenyl phosphate on the cytoplasmic side of the cell membrane by TagO and TagA, respectively[5]. Gro-P is CDP-activated by TagD and coupled to this disaccharide linkage unit by the primase TagB. In strains producing poly(Gro-P) WTA the final biosynthetic step involves the coupling of a large but variable amount of CDP-activated Gro-P monomers by the oligomerase TagF. Although TagF homologues (sometimes designated TarF) are present in several strains producing poly(Rbo-P) WTA, these enzymes are generally smaller than their TagF counterparts and their activity is limited to the incorporation of 1 or 2 additional CDP-activated Gro-P monomers[9, 62]. In the final biosynthetic steps CDP-activated Rbo-P, produced by TarJ and TarI, is added to the Gro-P mono-, di- or tri-mer by the primase (TarK) and the oligomerase activity (TarL), resulting in the addition of multiple repeating units of Rbo-P[5, 9, 13, 63]. Following its synthesis, the complete WTA polymer is proposed to be transported across the cytoplasmic membrane by the tagGH-encoded ABC transporter, and is subsequently coupled to the 6-hydroxyl of MurN Ac in peptidoglycan by an unknown transferase[5, 13]. These basic WTA polymers can be substituted with D-alanyl esters through the activity of the enzymes encoded in the dlt operon[31, 64, 65] and/or glycosyl moieties by homologues of TagE or TarM of B. subtilis and S. aureus, respectively[39, 40].