头状链霉菌中丝裂霉素C抗性基因mcrAB的克隆及其作用研究  

Cloning of mcrAB gene from Streptomyces caespitosus and study on the action of mcrAB

作　　者：王鲁燕[1] 朱春宝[2] 马文哲[1] 陈代杰[3] 许文思[2] 

机构地区：[1]中国药科大学,南京210009 [2]上海医药工业研究院,上海200040 [3]上海来益生物药物研究开发中心,上海201203

出　　处：《中国抗生素杂志》2002年第12期748-752,共5页Chinese Journal of Antibiotics

摘　　要：丝裂霉素 C属于苯醌类抗肿瘤抗生素 ,在生物体内作为前药 ,经酶催化还原后可阻碍 DNA的复制。我们从头状链霉菌中克隆出丝裂霉素 C抗性基因 mcr AB,测序结果与另一丝裂霉素产生菌—淡紫灰链霉菌的 mcr AB基因序列进行了比较 ,结果表明此序列是高度保守的。同时还构建了带有 mcr AB基因的质粒载体 p YG2 0 6 ,将 p YG2 0 6用原生质体转化法导入变青链霉菌 TK6 4 ,并在此菌中表达 ,大大提高了该菌对丝裂霉素 C的抗性。进一步研究表明 :在有氧条件下 ,mcr AB基因表达的蛋白可抑制菌体对丝裂霉素 C的转化作用。Mitomycin C (MMC) is an antitumor antibiotic containing quinone. MMC is a prodrug and requires an enzymatic reduction in vivo to interfere with DNA replication. The mcrAB gene was cloned from Streptomyces caespitosus , and the nucleotide sequences was compared with that of Streptomyces lavendulae . It revealed that mcrAB gene was highly conservative. Plasmid pYG206 containing mcrAB gene was constructed and introduced into Streptomyces lividans TK64 by protoplast transformation. The transformants appeared high level resistance to MMC. Further research showed that the protein encoded by mcrAB gene could inhibit transformation of MMC in the presence of O 2.

关 键 词：头状链霉菌 丝裂霉素C 抗性基因 mcrAB 克隆 作用 研究 抗肿瘤抗生素 

分 类 号：R979.14[医药卫生—药品]