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远端霉素合成基因簇下游基因dst27,dst28,dst29的初步探究

haracterization of distamycin biosynthesis cluster downstream genes: dst27,dst28,dst29

中文摘要英文摘要

远端霉素是纺锤链霉菌产生的一种抗生素,其能结合DNA小沟,且具有良好的抗病毒能力并极具抗癌潜力。其生物合成基因簇由两个不相邻的基因簇构成,其中簇1长约28 kb,簇2长约7 kb。本课题组在其簇2下游发现了三个此前未被关注的基因,并将其命名为dst27,dst28, dst29。生物信息学分析显示dst27,dst28, dst29与DNA修复/复制相关。进一步的实验表明dst27, dst28, dst29与纺锤链霉菌的产量相关,在纺锤链霉菌中敲除或过表达dst27,dst28, dst29都导致远端霉素的产量下降。生物信息学分析表明,dst27,dst28, dst29是三个DNA修复/复制有关的基因,与DNA结合类抗生素自我保护机制关系密切且其同源基因广泛地存在于DNA损伤类抗生素产生菌中,因此其可能代表着一类普遍存在但尚未被发现的DNA结合剂产生菌自我保护机制。

istamycin (DST) is a well-known DNA minor groove binder which is produced by Strptomyces netropsis. It has antivirus effect and antitumor potency. Cluster 1 (28 kb) and 2 (7 kb)have recently been identified to coordinately produce the DST. Here we report a gene cassette, which is linked to the smaller dst gene cluster could effect the production of DST. This cassette consists of three uncharacterized genes,namely dst27, dst28, dst29, In silico analyze shows these three genes are all associated with the DNA replication/repair. Knockout of the cassette led to decrease in DST production, while heterologous expression leds to a similar decrease in DST production. Homologs of these three genes also exist in genomes of other actinomyces that produce DNA-binding antibiotics.This phenomenon implies that dst27, dst28, dst29 may represent a common resistance mechanism in many DNA binding metabolites producers.

袁子雨、虞沂、马烈、孙思瑶

药学生物科学研究方法、生物科学研究技术分子生物学

微生物与生化药学生物合成自我保护机制远端霉素NA结合剂

Microbiology and Biochemical PharmacyBiosynthesisSelf-resistanceistamycinDNA damage agent

袁子雨,虞沂,马烈,孙思瑶.远端霉素合成基因簇下游基因dst27,dst28,dst29的初步探究[EB/OL].(2019-04-16)[2025-05-22].http://www.paper.edu.cn/releasepaper/content/201904-180.点此复制

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