Glycopeptide antitumor antibiotic zorbamycin from Streptomyces flavoviridis ATCC 21892: strain improvement and structure elucidation.
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.
Wang
Liyan
L
Division of Pharmaceutical Sciences, Microbiology Doctoral Training Program, Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53705, USA.
Yun
Bong-Sik
BS
George
Nicholas P
NP
Wendt-Pienkowski
Evelyn
E
Galm
Ute
U
Oh
Tae-Jin
TJ
Coughlin
Jane M
JM
Zhang
Guodong
G
Tao
Meifeng
M
Shen
Ben
B
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
D000903:Antibiotics, Antineoplastic; D006020:Glycopeptides; D009942:Organometallic Compounds; D003300:Copper; C003787:zorbamycin