title: Genetic insights into pyralomicin biosynthesis in Nonomuraea spiralis IMC A-0156.
abstract: The biosynthetic gene cluster for the pyralomicin antibiotics has been cloned and sequenced from Nonomuraea spiralis IMC A-0156. The 41 kb gene cluster contains 27 ORFs predicted to encode all of the functions for pyralomicin biosynthesis. This includes nonribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) required for the formation of the benzopyranopyrrole core unit, as well as a suite of tailoring enzymes (e.g., four halogenases, an O-methyltransferase, and an N-glycosyltransferase) necessary for further modifications of the core structure. The N-glycosyltransferase is predicted to transfer either glucose or a pseudosugar (cyclitol) to the aglycone. A gene cassette encoding C7-cyclitol biosynthetic enzymes was identified upstream of the benzopyranopyrrole-specific ORFs. Targeted disruption of the gene encoding the N-glycosyltransferase, prlH, abolished pyralomicin production, and recombinant expression of PrlA confirms the activity of this enzyme as a sugar phosphate cyclase involved in the formation of the C7-cyclitol moiety.
authors.affiliation: Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR 97331-3507, United States.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Flatt
authors.forename: Xiumei
authors.initials: X
authors.lastname: Wu
authors.forename: Steven
authors.initials: S
authors.lastname: Perry
authors.forename: Taifo
authors.initials: T
authors.lastname: Mahmud
mesh_terms: D039903:Actinobacteria / Q000235:genetics / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D002867:Chromones / Q000737:chemistry / Q000378:metabolism; D054812:Cyclitols / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005964:Glucosyltransferases / Q000378:metabolism; D015394:Molecular Structure; D005810:Multigene Family; D010453:Peptide Synthases / Q000378:metabolism; D048630:Polyketide Synthases / Q000378:metabolism; D011758:Pyrroles / Q000737:chemistry / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002867:Chromones; D054812:Cyclitols; D011758:Pyrroles; C101442:pyralomicin 1a; D048630:Polyketide Synthases; D005964:Glucosyltransferases; C410788:N-glycosyltransferase, Nocardia aerocolonigenes; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase