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Dissection of 3D chromosome organization in Streptomyces coelicolor A3(2) leads to biosynthetic gene cluster overexpression

文献类型： 外文期刊

作者： Liang Deng;Zhihu Zhao;Lin Liu;Zhiyu Zhong;Wenxinyu Xie;Fan Zhou;Wei Xu;Yubo Zhang;Zixin Deng;Yuhui Sun

作者机构：

关键词： chromosomal organization;Hi-C;natural products biosynthesis;Streptomyces

期刊名称： Proceedings of the National Academy of Sciences of the United States of America

ISSN： 0027-8424

年卷期： 2023 年 120 卷 11 期

页码：

收录情况： SCIE（2023版）

摘要： The soil-dwelling filamentous bacteria, Streptomyces, is widely known for its ability to produce numerous bioactive natural products. Despite many efforts toward their overproduction and reconstitution, our limited understanding of the relationship between the host's chromosome three dimension (3D) structure and the yield of the natural products escaped notice. Here, we report the 3D chromosome organization and its dynamics of the model strain, Streptomyces coelicolor, during the different growth phases. The chromosome undergoes a dramatic global structural change from primary to secondary metabolism, while some biosynthetic gene clusters (BGCs) form special local structures when highly expressed. Strikingly, transcription levels of endogenous genes are found to be highly correlated to the local chromosomal interaction frequency as defined by the value of the frequently interacting regions (FIREs). Following the criterion, an exogenous single reporter gene and even complex BGC can achieve a higher expression after being integrated into the chosen loci, which may represent a unique strategy to activate or enhance the production of natural products based on the local chromosomal 3D organization.

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