title: UDP-glucuronic acid decarboxylases of Bacteroides fragilis and their prevalence in bacteria.
abstract: Xylose is rarely described as a component of bacterial glycans. UDP-xylose is the nucleotide-activated form necessary for incorporation of xylose into glycans and is synthesized by the decarboxylation of UDP-glucuronic acid (UDP-GlcA). Enzymes with UDP-GlcA decarboxylase activity include those that lead to the formation of UDP-xylose as the end product (Uxs type) and those synthesizing UDP-xylose as an intermediate (ArnA and RsU4kpxs types). In this report, we identify and confirm the activities of two Uxs-type UDP-GlcA decarboxylases of Bacteroides fragilis, designated BfUxs1 and BfUxs2. Bfuxs1 is located in a conserved region of the B. fragilis genome, whereas Bfuxs2 is in the heterogeneous capsular polysaccharide F (PSF) biosynthesis locus. Deletion of either gene separately does not result in the loss of a detectable phenotype, but deletion of both genes abrogates PSF synthesis, strongly suggesting that they are functional paralogs and that the B. fragilis NCTC 9343 PSF repeat unit contains xylose. UDP-GlcA decarboxylases are often annotated incorrectly as NAD-dependent epimerases/dehydratases; therefore, their prevalence in bacteria is underappreciated. Using available structural and mutational data, we devised a sequence pattern to detect bacterial genes encoding UDP-GlcA decarboxylase activity. We identified 826 predicted UDP-GlcA decarboxylase enzymes in diverse bacterial species, with the ArnA and RsU4kpxs types confined largely to proteobacterial species. These data suggest that xylose, or a monosaccharide requiring a UDP-xylose intermediate, is more prevalent in bacterial glycans than previously appreciated. Genes encoding BfUxs1-like enzymes are highly conserved in Bacteroides species, indicating that these abundant intestinal microbes may synthesize a conserved xylose-containing glycan.
authors.affiliation: Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Coyne
authors.forename: C Mark
authors.initials: CM
authors.lastname: Fletcher
authors.forename: Barbara
authors.initials: B
authors.lastname: Reinap
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Comstock
mesh_terms: D001441:Bacteroides fragilis / Q000201:enzymology* / Q000378:metabolism; D015153:Blotting, Western; D002262:Carboxy-Lyases / Q000235:genetics / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D019295:Computational Biology; D004591:Electrophoresis, Polyacrylamide Gel; D016680:Genome, Bacterial / Q000235:genetics; D011135:Polysaccharides, Bacterial / Q000378:metabolism; D014994:Xylose / Q000378:metabolism
chemical_list: D011135:Polysaccharides, Bacterial; D014994:Xylose; D002262:Carboxy-Lyases; C023257:UDPglucuronate decarboxylase