Isolation and characterization of novel geldanamycin analogues

被引:17
作者
Hu, ZH [1 ]
Liu, YQ [1 ]
Tian, ZQ [1 ]
Ma, W [1 ]
Starks, CM [1 ]
Regentin, R [1 ]
Licari, P [1 ]
Myles, DC [1 ]
Hutchinson, CR [1 ]
机构
[1] Kosan Biosci Inc, Hayward, CA 94545 USA
关键词
D O I
10.7164/antibiotics.57.421
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
New geldanamycin analogues with novel structures arising from direct microbial bioconversion and a genetically engineered geldanamycin producer were isolated and characterized. Three compounds, 15-hydroxygeldanamycin, a tricyclic geldanamycin analog (KOSN-1633), and methyl-geldanamycinate(1)), were isolated after geldanamycin was added to a growing culture of the herbimycin producing strain-Streptomyces hygroscopicus AM-3672. Two related compounds, 17-formyl-17-demethoxy-18-O,-21-O-dihydrogeldanamycin and 17-hydroxymethyl-17-demethoxygeldanamycin were isolated from S. hygroscopicus NRRL 3602/pKOS279-78, a geldanamycin-producing strain containing various genes isolated from S. hygroscopicus AM-3672. Compared with geldanamycin, these five new compounds exhibited reduced cytotoxicity against SKBr3 cancer cells.
引用
收藏
页码:421 / 428
页数:8
相关论文
共 15 条
[1]   PLASMID CLONING VECTORS FOR THE CONJUGAL TRANSFER OF DNA FROM ESCHERICHIA-COLI TO STREPTOMYCES SPP [J].
BIERMAN, M ;
LOGAN, R ;
OBRIEN, K ;
SENO, ET ;
RAO, RN ;
SCHONER, BE .
GENE, 1992, 116 (01) :43-49
[2]   MICROBIAL CONVERSION OF GRISORIXIN, A MONO-VALENT CATION IONOPHOROUS ANTIBIOTIC [J].
CUER, A ;
DAUPHIN, G ;
BELOEIL, JC .
JOURNAL OF ANTIBIOTICS, 1983, 36 (01) :20-24
[3]   GELDANAMYCIN, A NEW ANTIBIOTIC [J].
DEBOER, C ;
MEULMAN, PA ;
WNUK, RJ ;
PETERSON, DH .
JOURNAL OF ANTIBIOTICS, 1970, 23 (09) :442-&
[4]   DESCRIPTION AND ANTIBIOTIC PRODUCTION OF STREPTOMYCES-HYGROSCOPICUS VAR GELDANUS [J].
DEBOER, C ;
DIETZ, A .
JOURNAL OF ANTIBIOTICS, 1976, 29 (11) :1182-1188
[5]   High efficiency intergeneric conjugal transfer of plasmid DNA from Escherichia coli to methyl DNA-restricting streptomycetes [J].
Flett, F ;
Mersinias, V ;
Smith, CP .
FEMS MICROBIOLOGY LETTERS, 1997, 155 (02) :223-229
[6]   Performance of a recombinant strain of Streptomyces lividans for bioconversion of penicillin G to deacetoxycephalosporin G [J].
Gao, Q ;
Piret, JM ;
Adrio, JL ;
Demain, AL .
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY, 2003, 30 (03) :190-194
[7]  
Kieser T., 2000, PRACTICAL STREPTOMYC, DOI DOI 10.1111/J.1365-2427.2007.01876.X
[8]  
Kuhnt M, 1998, APPL ENVIRON MICROB, V64, P714
[9]   Hsp90 inhibitors as novel cancer chemotherapeutic agents [J].
Neckers, L .
TRENDS IN MOLECULAR MEDICINE, 2002, 8 (04) :S55-S61
[10]   Bioconversion of milbemycin-related compounds: Biosynthetic pathway of milbemycins [J].
Nonaka, K ;
Kumasaka, C ;
Okamoto, Y ;
Maruyama, F ;
Yoshikawa, H .
JOURNAL OF ANTIBIOTICS, 1999, 52 (02) :109-116