title: Glycopeptide antitumor antibiotic zorbamycin from Streptomyces flavoviridis ATCC 21892: strain improvement and structure elucidation.
abstract: Zorbamycin (1, ZBM) is a glycopeptide antitumor antibiotic first reported in 1971. The partial structures of 1 were speculated on the basis of its acid hydrolysis products, but the structure of the intact molecule has never been established. The low titer of 1 from the wild-type strain, combined with its acid-instability, has so far hampered its isolation. By random mutagenesis of Streptomyces flavoviridis ATCC21892, a wild-type producer of 1, with UV irradiation, two high-producing strains of 1, S. flavoviridis SB9000 and SB9001, were isolated. Under the optimized fermentation conditions, these two strains produced about 10 mg/L of 1, which was about 10-fold higher than the wild-type ATCC21892 strain, as estimated by HPLC analysis. Finally, 1 was isolated as both a 1-Cu complex and Cu-free molecule, and the intact structure of 1 was established on the basis of a combination of mass spectrometry and 1H and 13C NMR spectroscopic analyses.
authors.affiliation: Division of Pharmaceutical Sciences, Microbiology Doctoral Training Program, Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Liyan
authors.initials: L
authors.lastname: Wang
authors.forename: Bong-Sik
authors.initials: BS
authors.lastname: Yun
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: George
authors.forename: Evelyn
authors.initials: E
authors.lastname: Wendt-Pienkowski
authors.forename: Ute
authors.initials: U
authors.lastname: Galm
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Oh
authors.forename: Jane M
authors.initials: JM
authors.lastname: Coughlin
authors.forename: Guodong
authors.initials: G
authors.lastname: Zhang
authors.forename: Meifeng
authors.initials: M
authors.lastname: Tao
authors.forename: Ben
authors.initials: B
authors.lastname: Shen
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D003300:Copper / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006020:Glycopeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015394:Molecular Structure; D016296:Mutagenesis / Q000528:radiation effects; D009942:Organometallic Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013302:Streptomyces / Q000737:chemistry* / Q000235:genetics / Q000528:radiation effects
chemical_list: D000903:Antibiotics, Antineoplastic; D006020:Glycopeptides; D009942:Organometallic Compounds; D003300:Copper; C003787:zorbamycin