title: Quinovosamycins: new tunicamycin-type antibiotics in which the α, β-1″,11'-linked N-acetylglucosamine residue is replaced by N-acetylquinovosamine.
abstract: Tunicamycins (TUN) are potent inhibitors of polyprenyl phosphate N-acetylhexosamine 1-phosphate transferases (PPHP), including essential eukaryotic GPT enzymes and bacterial HexNAc 1-P translocases. Hence, TUN blocks the formation of eukaryotic N-glycoproteins and the assembly of bacterial call wall polysaccharides. The genetic requirement for TUN production is well-established. Using two genes unique to the TUN pathway (tunB and tunD) as probes we identified four new prospective TUN-producing strains. Chemical analysis showed that one strain, Streptomyces niger NRRL B-3857, produces TUN plus new compounds, named quinovosamycins (QVMs). QVMs are structurally akin to TUN, but uniquely in the 1″,11'-HexNAc sugar head group, which is invariably d-GlcNAc for the known TUN, but is d-QuiNAc for the QVM. Surprisingly, this modification has only a minor effect on either the inhibitory or antimicrobial properties of QVM and TUN. These findings have unexpected consequences for TUN/QVM biosynthesis, and for the specificity of the PPHP enzyme family.
authors.affiliation: Renewable Products Technology Unit, National Center for Agricultural Utilization Research, USDA-ARS, Peoria, IL, USA.
authors.forename: Neil Pj
authors.initials: NP
authors.lastname: Price
authors.affiliation: Mycotoxin Prevention and Applied Microbiology Unit, National Center for Agricultural Utilization Research, USDA-ARS, Peoria, IL, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Labeda
authors.affiliation: Mycotoxin Prevention and Applied Microbiology Unit, National Center for Agricultural Utilization Research, USDA-ARS, Peoria, IL, USA.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Naumann
authors.affiliation: Functional Foods Unit, National Center for Agricultural Utilization Research, USDA-ARS, Peoria, IL, USA.
authors.forename: Karl E
authors.initials: KE
authors.lastname: Vermillion
authors.affiliation: Bioenergy Research Unit, National Center for Agricultural Utilization Research, USDA-ARS, Peoria, IL, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bowman
authors.affiliation: Functional Foods Unit, National Center for Agricultural Utilization Research, USDA-ARS, Peoria, IL, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Berhow
authors.affiliation: Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.|Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Metcalf
authors.affiliation: Renewable Products Technology Unit, National Center for Agricultural Utilization Research, USDA-ARS, Peoria, IL, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Bischoff
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005944:Glucosamine / Q000031:analogs & derivatives / Q000737:chemistry; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*; D014415:Tunicamycin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D014415:Tunicamycin; D005944:Glucosamine; C009149:6-desoxy-D-glucosamine; D000117:Acetylglucosamine