PRODUCTION AND BIOLOGICAL-ACTIVITY OF REBECCAMYCIN, A NOVEL ANTITUMOR AGENT
PRODUCTION AND BIOLOGICAL-ACTIVITY OF REBECCAMYCIN, A NOVEL ANTITUMOR AGENT
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DOI：
10.7164/antibiotics.40.668
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发表时间：
1987-05-01
影响因子：
3.3
通讯作者：
BRADNER, WT
中科院分区：
文献类型：
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作者：
BUSH, JA;LONG, BH;BRADNER, WT
筛选出一株放线菌，菌株C-38,383，用于分离新的抗肿瘤药物。从菌丝体中分离到一种黄色结晶产物，命名为瑞贝卡霉素，并发现它对小鼠移植的P388白血病、L1210白血病和B16黑色素瘤具有活性。瑞贝卡霉素抑制人肺腺癌细胞(A549)的生长，并在这些细胞的DNA中产生单链断裂。未检测到DNA-蛋白质交联物。一种相关的抗生素，星形孢子素，是由STaurosporeus和Streptomyces Actuosus产生的。菌株C-38,383被发现与新近更名为Saccharothrix Aerocoloniges的诺卡氏菌非常相似。一株无气生菌丝的菌株C-38,383-RK-1不能产生瑞贝卡霉素，而有气生菌丝的菌株C-38,383-RK-2适合生产。对产生菌进行了描述，并对其分类地位进行了综述。在37升发酵罐中，菌株C-38,383-RK-2发酵204小时后，雷贝卡霉素产量为663 mg/L。
An actinomycete, strain C-38,383, was selected in a screening program for the isolation of novel antitumor agents. A yellow crystalline product, named rebeccamycin, was isolated from the mycelium and was found to have activity against P388 leukemia, L1210 leukemia and B16 melanoma implanted in mice. Rebeccamycin inhibits the growth of human lung adenocarcinoma cells (A549) and produces single-strand breaks in the DNA of these cells. No DNA-protein cross-links were detected. A related antibiotic, staurosporine, is produced by Streptomyces staurosporeus and Streptomyces actuosus. Strain C-38,383 was found to resemble closely strains of Nocardia aerocolonigenes recently renamed Saccharothrix aerocolonigenes. A strain selection isolate without aerial mycelium, C-38,383-RK-1, failed to produce rebeccamycin while a strain with aerial mycelium, C-38,383-RK-2, was found to be a suitable strain for production. A description of the producing strain is presented and its taxonomic position is reviewed. A fermentor containing 37 liters of production medium gave a rebeccamycin yield of 663 mg/liter after 204 hours of incubation with strain C-38,383-RK-2.