Discovery of Alternative Producers of the Enediyne Antitumor Antibiotic C-1027 with High Titers.
Discovery of Alternative Producers of the Enediyne Antitumor Antibiotic C-1027 with High Titers.
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DOI：
10.1021/acs.jnatprod.7b01013
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发表时间：
2018-03-23
影响因子：
5.1
通讯作者：
Shen B
中科院分区：
文献类型：
--
作者：
Yan X;Hindra;Ge H;Yang D;Huang T;Crnovcic I;Chang CY;Fang SM;Annaval T;Zhu X;Huang Y;Zhao LX;Jiang Y;Duan Y;Shen B
烯二炔类抗肿瘤抗生素C-1027具有很强的细胞毒性和独特的作用机制，是一种优良的抗癌化疗候选药物。然而，C-1027的临床开发由于其来自原始生产者球孢链霉菌C-1027的低滴度而受到阻碍。在这里，我们报告了三个新的C-1027替代生产商，链霉菌属CB 00657，CB 02329和CB 03608，从斯克里普斯研究所放线菌菌株收藏。与先前公开的链霉菌属CB 02366菌株一起，已经发现了四种C-1027替代生产者，其C-1027滴度比原始生产者高高达11倍。从遥远的地理位置分离的五个C-1027生产者是基于形态学和分类学的不同链霉菌菌株。脉冲场凝胶电泳和Southern分析的五个C-1027生产商显示，他们的C-1027生物合成基因簇（BGC）都位于不同大小的巨型质粒。5个C-1027 BGC之间的高核苷酸序列相似性意味着它们很可能是从共同的祖先进化而来的。
The potent cytotoxicity and unique mode of action make the enediyne antitumor antibiotic C-1027 an exquisite drug candidate for anticancer chemotherapy. However, clinical development of C-1027 has been hampered by its low titer from the original producer Streptomyces globisporus C-1027. Here we report three new C-1027 alternative producers, Streptomyces sp. CB00657, CB02329, and CB03608, from The Scripps Research Institute actino-mycetes strain collection. Together with the previously disclosed Streptomyces sp. CB02366 strain, four C-1027 alternative producers with C-1027 titers of up to 11-fold higher than the original producer have been discovered. The five C-1027 producers, isolated from distant geographic locations, are distinct Streptomyces strains based on morphology and taxonomy. Pulsed-field gel electrophoresis and Southern analysis of the five C-1027 producers reveal that their C-1027 biosynthetic gene clusters (BGCs) are all located on giant plasmids of varying sizes. The high nucleotide sequence similarity among the five C-1027 BGCs implies that they most likely have evolved from a common ancestor.
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DOI：
10.1038/ja.2010.55
发表时间：
2010-08
期刊：
The Journal of antibiotics
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.1
作者：
Xie P;Ma M;Rateb ME;Shaaban KA;Yu Z;Huang SX;Zhao LX;Zhu X;Yan Y;Peterson RM;Lohman JR;Yang D;Yin M;Rudolf JD;Jiang Y;Duan Y;Shen B
通讯作者：
Shen B
利福霉素小单孢菌 (Micromonospora rifamycinica sp nov.)，一种来自红树林沉积物的新型放线菌
DOI：
10.1099/ijs.0.64484-0
发表时间：
2008-01-01
影响因子：
2.8
作者：
Huang, Huiqin;Lv, Jiasen;Bao, Shixiang
通讯作者：
Bao, Shixiang
影响因子：
3.2
作者：
Yamasaki, M;Kinashi, H
通讯作者：
Kinashi, H
DOI：
10.1073/pnas.0708274104
发表时间：
2007-11-06
影响因子：
11.1
作者：
Kennedy, Daniel R.;Ju, Jianhua;Beerman, Terry A.
通讯作者：
Beerman, Terry A.