title: MoeH5: a natural glycorandomizer from the moenomycin biosynthetic pathway.
abstract: The biosynthesis of the phosphoglycolipid antibiotic moenomycin A attracts the attention of researchers hoping to develop new moenomycin-based antibiotics against multidrug resistant Gram-positive infections. There is detailed understanding of most steps of this biosynthetic pathway in Streptomyces ghanaensis (ATCC14672), except for the ultimate stage, where a single pentasaccharide intermediate is converted into a set of unusually modified final products. Here we report that only one gene, moeH5, encoding a homologue of the glutamine amidotransferase (GAT) enzyme superfamily, is responsible for the observed diversity of terminally decorated moenomycins. Genetic and biochemical evidence support the idea that MoeH5 is a novel member of the GAT superfamily, whose homologues are involved in the synthesis of various secondary metabolites as well as K and O antigens of bacterial lipopolysaccharide. Our results provide insights into the mechanism of MoeH5 and its counterparts, and give us a new tool for the diversification of phosphoglycolipid antibiotics.
authors.affiliation: Department of Genetics and Biotechnology, Ivan Franko National University of Lviv, 4 Hrushevskoho st., Lviv, 79005, Ukraine; Department of Microbiology and Immunobiology, Harvard Medical School, 4 Blackfan Circle, Boston, MA, 02115, USA.
authors.forename: Bohdan
authors.initials: B
authors.lastname: Ostash
authors.forename: Jennifer
authors.initials: J
authors.lastname: Campbell
authors.forename: Andriy
authors.initials: A
authors.lastname: Luzhetskyy
authors.forename: Suzanne
authors.initials: S
authors.lastname: Walker
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001455:Bambermycins / Q000096:biosynthesis*; D053898:Biosynthetic Pathways; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D005798:Genes, Bacterial; D005810:Multigene Family; D010802:Phylogeny; D064210:Secondary Metabolism; D017386:Sequence Homology, Amino Acid; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001455:Bambermycins