Identification of 4,5-Dihydro-4-hydroxygeldanamycins As Shunt Products of Geldanamycin Biosynthesis

被引：18

作者：

Li, Ting

Ni, Siyang

Jia, Changhong

Wang, Hongyuan

Sun, Guizhi

Wu, Linzhuan ^{[1
]}

Gan, Maoluo

Shan, Guangzhi

He, Weiqing

Lin, Ling

Zhou, Hongxia

Wang, Yiguang

机构：

[1] Peking Union Med Coll, Key Lab Biotechnol Antibiot, Minist Hlth, Inst Med Biotechnol, Beijing 100050, Peoples R China

来源：

JOURNAL OF NATURAL PRODUCTS | 2012年 / 75卷 / 08期

基金：

中国国家自然科学基金;

关键词：

STREPTOMYCES-HYGROSCOPICUS; 17997; ANTITUMOR AGENT; ABSOLUTE-CONFIGURATION; DERIVATIVES; ANALOGS; INHIBITION; POLYKETIDE; ALCOHOLS; STRAIN;

D O I：

10.1021/np3001738

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

Two new geldanamycin (GDM) analogues, (4S)-4,5-dihydro-4-hydroxygeldanamycin (1) and (4R)-4,5-dihydro-4-hydroxygeldanamycin (2), were identified from Streptomyces hygroscopicus 17997. Compounds 1 and 2 were not normal intermediates of GDM biosynthesis but shunt Products of C-4,5 oxidation catalyzed by GdmP, a cytochrome P450 oxidase acting as a desaturase in GDM biosynthesis. Preliminary assays implied that, Compared with GDM, 1 and 2 exhibited decreased cytotoxicity.

引用

页码：1480 / 1484

页数：5

共 26 条

[1]

BeBoer C, 1976, J Antibiot (Tokyo), V29, P1182

[2] Production of 8-demethylgeldanamycin and 4,5-epoxy-8-demethylgeldanamycin from a recombinant strain of Streptomyces hygroscopicus [J].

Buchanan, GO ;

Regentin, R ;

Piagentini, M ;

Rascher, A ;

McDaniel, R ;

Galazzo, JL ;

Licari, PJ .

JOURNAL OF NATURAL PRODUCTS, 2005, 68 (04) :607-610

[3] New, Highly Active Nonbenzoquinone Geldanamycin Derivatives by Using Mutasynthesis [J].

Eichner, Simone ;

Floss, Heinz G. ;

Sasse, Florenz ;

Kirschning, Andreas .

CHEMBIOCHEM, 2009, 10 (11) :1801-1805

[4] Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity [J].

Guengerich, FP .

CHEMICAL RESEARCH IN TOXICOLOGY, 2001, 14 (06) :611-650

[5]

HASSNER A, 1978, TETRAHEDRON LETT, P4475

[6]

He Weiqing, 2008, Sheng Wu Gong Cheng Xue Bao, V24, P1133

[7] Inactivation of the carbamoyltransferase gene refines post-polyketide synthase modification steps in the biosynthesis of the antitumor agent geldanamycin [J].

Hong, YS ;

Lee, D ;

Kim, W ;

Jeong, JK ;

Kim, CG ;

Sohng, JK ;

Lee, JH ;

Paik, SG ;

Lee, JJ .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (36) :11142-11143

[8] Isolation and characterization of novel geldanamycin analogues [J].

Hu, ZH ;

Liu, YQ ;

Tian, ZQ ;

Ma, W ;

Starks, CM ;

Regentin, R ;

Licari, P ;

Myles, DC ;

Hutchinson, CR .

JOURNAL OF ANTIBIOTICS, 2004, 57 (07) :421-428

[9] GELDANAMYCIN BIOSYNTHESIS AND CARBON MAGNETIC-RESONANCE [J].

JOHNSON, RD ;

HABER, A ;

RINEHART, KL .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1974, 96 (10) :3316-3317

[10] Rational Biosynthetic Engineering for Optimization of Geldanamycin Analogues [J].

Kim, Woncheol ;

Lee, Dongho ;

Hong, Seong Su ;

Na, Zhu ;

Shin, Jin Chul ;

Roh, Su Heun ;

Wu, Cheng-Zhu ;

Choi, Oksik ;

Lee, Kyeong ;

Shen, Yue-Mao ;

Paik, Sang-Gi ;

Lee, Jung Joon ;

Hong, Young-Soo .

CHEMBIOCHEM, 2009, 10 (07) :1243-1251

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