title: Biosynthesis of the Peptide Antibiotic Feglymycin by a Linear Nonribosomal Peptide Synthetase Mechanism.
abstract: Feglymycin, a peptide antibiotic produced by Streptomyces sp. DSM 11171, consists mostly of nonproteinogenic phenylglycine-type amino acids. It possesses antibacterial activity against methicillin-resistant Staphylococcus aureus strains and antiviral activity against HIV. Inhibition of the early steps of bacterial peptidoglycan synthesis indicated a mode of action different from those of other peptide antibiotics. Here we describe the identification and assignment of the feglymycin (feg) biosynthesis gene cluster, which codes for a 13-module nonribosomal peptide synthetase (NRPS) system. Inactivation of an NRPS gene and supplementation of a hydroxymandelate oxidase mutant with the amino acid l-Hpg proved the identity of the feg cluster. Feeding of Hpg-related unnatural amino acids was not successful. This characterization of the feg cluster is an important step to understanding the biosynthesis of this potent antibacterial peptide.
authors.affiliation: Institut für Chemie, Technische Universität BerlinStrasse des 17. Juni 124, 10623, Berlin, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Gonsior
authors.affiliation: Institut für Chemie, Technische Universität BerlinStrasse des 17. Juni 124, 10623, Berlin, Germany.
authors.forename: Agnes
authors.initials: A
authors.lastname: Mühlenweg
authors.affiliation: Institut für Chemie, Technische Universität BerlinStrasse des 17. Juni 124, 10623, Berlin, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Tietzmann
authors.affiliation: Institut für Chemie, Technische Universität BerlinStrasse des 17. Juni 124, 10623, Berlin, Germany.
authors.forename: Saskia
authors.initials: S
authors.lastname: Rausch
authors.affiliation: Institut für Chemie, Technische Universität BerlinStrasse des 17. Juni 124, 10623, Berlin, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Poch
authors.affiliation: Institut für Chemie, Technische Universität BerlinStrasse des 17. Juni 124, 10623, Berlin, Germany. suessmuth@chem.tu-berlin.de.
authors.forename: Roderich D
authors.initials: RD
authors.lastname: Süssmuth
mesh_terms: D000900:Anti-Bacterial Agents / Q000032:analysis / Q000096:biosynthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D013058:Mass Spectrometry; D005810:Multigene Family; D016366:Open Reading Frames / Q000235:genetics; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D011506:Proteins; C120179:feglymycin; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase
keywords: antibiotics; cell-wall biosynthesis inhibitor; dihydroxyphenylglycine; hydroxyphenylglycine; nonribosomal peptide synthesis; peptides