title: Investigating beta-hydroxyenduracididine formation in the biosynthesis of the mannopeptimycins.
abstract: The mannopeptimycins (MPPs) are potent glycopeptide antibiotics that contain both D and L forms of the unique, arginine-derived amino acid beta-hydroxyenduracididine (betahEnd). The product of the mppO gene in the MPP biosynthetic cluster resembles several non-heme iron, alpha-ketoglutarate-dependent oxygenases, such as VioC and clavaminate synthase. The role of MppO in betahEnd biosynthesis was confirmed through inactivation of mppO, which yielded a strain that produced dideoxy-MPPs, indicating that mppO is essential for generating the beta-hydroxy functionality for both betahEnd residues. Characterization in vitro of recombinant His6-MppO expressed in E. coli revealed that MppO selectively hydroxylates the beta carbon of free L-enduracididine.
authors.affiliation: Natural Products Discovery, Wyeth Research, Pearl River, New York 10965, USA. haltlib@wyeth.com
authors.forename: Brad
authors.initials: B
authors.lastname: Haltli
authors.forename: Ying
authors.initials: Y
authors.lastname: Tan
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Magarvey
authors.forename: Melissa
authors.initials: M
authors.lastname: Wagenaar
authors.forename: Xihou
authors.initials: X
authors.lastname: Yin
authors.forename: Michael
authors.initials: M
authors.lastname: Greenstein
authors.forename: John A
authors.initials: JA
authors.lastname: Hucul
authors.forename: T Mark
authors.initials: TM
authors.lastname: Zabriskie
mesh_terms: D000596:Amino Acids / Q000737:chemistry* / Q000378:metabolism*; D006020:Glycopeptides / Q000096:biosynthesis* / Q000737:chemistry; D048289:Imidazolidines / Q000737:chemistry* / Q000378:metabolism*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009154:Mutation / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013302:Streptomyces / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
chemical_list: D000596:Amino Acids; D006020:Glycopeptides; D048289:Imidazolidines; C508265:beta-hydroxyenduracididine; C478082:mannopeptimycin