Glycopeptide Antitumor Antibiotic Zorbamycin from Streptomyces flavoviridis ATCC 21892: Strain Improvement and Structure Elucidation

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• 作者：Liyan Wang ; Bong-Sik Yun ; Nicholas P. George ; Evelyn Wendt-Pienkowski ; Ute Galm ; Tae-Jin Oh ; Jane M. Coughlin ; Guodong Zhang ; Meifeng Tao ; Ben Shen
• 刊名：Journal of Natural Products
• 出版年：2007
• 出版时间：March 2007
• 年：2007
• 卷：70
• 期：3
• 页码：402 - 406
• 全文大小：109K
• 年卷期：v.70,no.3(March 2007)
• ISSN：1520-6025

文摘

Zorbamycin (1, ZBM) is a glycopeptide antitumor antibiotic first reported in 1971. The partial structures of 1 werespeculated 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. Byrandom mutagenesis of Streptomyces flavoviridis ATCC21892, a wild-type producer of 1, with UV irradiation, twohigh-producing strains of 1, S. flavoviridis SB9000 and SB9001, were isolated. Under the optimized fermentationconditions, these two strains produced about 10 mg/L of 1, which was about 10-fold higher than the wild-type ATCC21892strain, as estimated by HPLC analysis. Finally, 1 was isolated as both a 1-Cu complex and Cu-free molecule, and theintact structure of 1 was established on the basis of a combination of mass spectrometry and ¹H and ¹³C NMR spectroscopicanalyses.