This schematic is based largely on the work of Schoenhofen et. al. Please refer to [14, 18] and references within for more detailed descriptions of the enzymes and intermediates of these pathways. Phylogenetic comparisons were performed to provide additional insights into the potential functions of Leptospira nonulosonic acid biosynthesis enzymes. We included in the phylogenetic Veliparib purchase analysis the well-characterized enzymes of Campylobacter jejuni that participate in parallel pathways of legionamimic, pseudaminic, and neuraminic acid synthesis [14, 17–21]. A schematic of these biosynthetic pathways is shown in Figure 5, noting the structural differences between neuraminic (sialic), legionamimic, and pseudaminic

Ro 61-8048 cell line acids. These different NulOs are used by C. jejuni to modify a variety of different surface structures including the O-antigen of lipooligosaccharides, flagellin, and other surface proteins. To add further resolution to our

phylogenetic analysis, we also included NulO biosynthetic enzymes from two Photobacterium profundum genome strains (3TCK and SS9), previously demonstrated to synthesize legionamimic and pseudaminic acids respectively [16]. In addition, homologous enzymes from other Leptospira genomes (L. noguchii str. 2006001870, L. biflexa serovar Patoc, L. santarosai str. 2000030832, L. borgpetersenii serovar Hardjo-bovis str. L550) were included in the phylogenetic analysis to better place the L. interrogans NulO enzymes into context with other putative leptospiral NulO biosynthetic enzymes. The phylogenetic analysis

of L. interrogans NulO biosynthetic www.selleckchem.com/products/cx-5461.html enzymes demonstrates PRKD3 that a subset of these enzymes is more closely related to the C. jejuni legionaminic acid biosynthetic enzymes and more distantly related to the pseudaminic acid biosynthetic enzymes (Figure 6). Specifically, the aminotransferases YP_002110 and NP_711788 and the NulO synthetases YP_002108 and NP_711790 in L. interrogans serovars Copenhageni and Lai respectively, are more closely related to legionaminic acid synthesis enzymes and more distantly related to C. jejuni and P. profundum pseudaminic acid synthesis enzymes (Figure 6A-B, note green and pink shading indicates legionaminic acid pseudaminic acid pathways respectively). A similar relationship was found for the predicted epimerase/NDP-sugar hydrolases YP_002107 and NP_711791(not shown). Moreover, we find that both homologs of the putative CMP-NulO synthetases in L. interrogans (YP_002102 and YP_002112 in L1-130 and NP_711786 and NP_711796 in 56601) are more closely related to legionaminic acid and neuraminic acid synthetases than to CMP-pseudaminic acid synthetases (Figure 6C). Note in this figure that CMP-Kdo synthases were included to provide contrast and distinguish between enzymes that likely participate in CMP activation of eight carbon sugars (i.e. Kdo) and nine carbon sugars (i.e. NulOs).