The Transcriptional Regulator DhyR Positively Modulates Daptomycin Biosynthesis in Streptomyces roseosporus

IF 5.7 2区 生物学
Fuqiang He, Xinpeng Liu, Haiyi Wang, Xu Li, Yun Wu, Dan Zhang, Shufang Liang
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引用次数: 0

Abstract

Daptomycin (DAP) is a cyclic lipopeptide antibiotic produced by Streptomyces roseosporus, and its biosynthesis is precisely regulated by a complex regulatory network. Although the biosynthetic pathway of DAP has been elucidated, the regulatory mechanism governing its biosynthesis at the transcriptional level is not yet fully understood. In the present study, a new transcriptional regulator, DhyR, was identified. A deletion mutant of dhyR was constructed using the CRISPR-Cas9 tool to elucidate the biological role of DhyR thanks to functional and transcriptomic analyses. The results demonstrated that DhyR positively regulates DAP biosynthesis in S. roseosporus. The in-frame deletion of the dhyR gene resulted in a significant downregulation of the transcription levels of all structural genes within the DAP biosynthetic gene cluster and a significant decrease in DAP yield. In contrast, overexpression of dhyR enhanced the transcription levels of the DAP biosynthetic gene cluster, leading to a 23% increase in DAP yield. Deletion of dhyR caused significant changes in the expression of multiple genes involved in carbohydrate metabolism, energy metabolism and amino acid metabolic pathways through transcriptome analysis. Especially, deletion of dhyR led to a significant downregulation of transcription levels of three DAP biosynthesis-associated genes, including atrA, depR1 and ssig-05090. In summary, DhyR positively regulates DAP biosynthesis in S. roseosporus by influencing the expression of the DAP gene cluster and modulating precursor flux. It functions as a pleiotropic regulator of primary and secondary metabolism in S. roseosporus.

Abstract Image

转录调节因子DhyR正调控玫瑰孢链霉菌达托霉素的生物合成
达托霉素(Daptomycin, DAP)是由玫瑰孢链霉菌(Streptomyces rosesporus)产生的环脂肽类抗生素,其生物合成受到复杂的调控网络的精确调控。虽然已经阐明了DAP的生物合成途径,但在转录水平上调控其生物合成的调控机制尚不完全清楚。在本研究中,发现了一个新的转录调控因子,DhyR。利用CRISPR-Cas9工具构建了dhyR的缺失突变体,通过功能和转录组学分析阐明了dhyR的生物学作用。结果表明,DhyR正调控玫瑰孢菌DAP的生物合成。dhyR基因的框内缺失导致DAP生物合成基因簇内所有结构基因的转录水平显著下调,DAP产量显著降低。相比之下,过表达dhyR提高了DAP生物合成基因簇的转录水平,导致DAP产量增加23%。通过转录组分析,dhyR的缺失导致与碳水化合物代谢、能量代谢和氨基酸代谢途径相关的多个基因的表达发生显著变化。特别是,dhyR的缺失导致三种DAP生物合成相关基因的转录水平显著下调,包括atrA、depR1和sign -05090。综上所述,DhyR通过影响DAP基因簇的表达和调节前体通量,正向调节玫瑰孢葡萄中DAP的生物合成。它是玫瑰孢酵母初级和次级代谢的多效调节剂。
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来源期刊
Microbial Biotechnology
Microbial Biotechnology Immunology and Microbiology-Applied Microbiology and Biotechnology
CiteScore
11.20
自引率
3.50%
发文量
162
审稿时长
1 months
期刊介绍: Microbial Biotechnology publishes papers of original research reporting significant advances in any aspect of microbial applications, including, but not limited to biotechnologies related to: Green chemistry; Primary metabolites; Food, beverages and supplements; Secondary metabolites and natural products; Pharmaceuticals; Diagnostics; Agriculture; Bioenergy; Biomining, including oil recovery and processing; Bioremediation; Biopolymers, biomaterials; Bionanotechnology; Biosurfactants and bioemulsifiers; Compatible solutes and bioprotectants; Biosensors, monitoring systems, quantitative microbial risk assessment; Technology development; Protein engineering; Functional genomics; Metabolic engineering; Metabolic design; Systems analysis, modelling; Process engineering; Biologically-based analytical methods; Microbially-based strategies in public health; Microbially-based strategies to influence global processes
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