Influence of Cluster-Situated Regulator PteF in Filipin Biosynthetic Cluster on Avermectin Biosynthesis in Streptomyces avermitilis

文献类型： 外文期刊

第一作者： Du, Guozhong

作者： Du, Guozhong;Yang, Xue;Wu, Zhengxiong;Pan, Minghui;Dong, Zhuoxu;Zhang, Yanyan;Xiang, Wensheng;Li, Shanshan;Pan, Minghui;Dong, Zhuoxu;Xiang, Wensheng

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关键词： avermectin; filipin; regulator; Streptomyces avermitilis; transcriptome

期刊名称：BIOLOGY-BASEL （ 影响因子：4.2； 五年影响因子：4.4 ）

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年卷期： 2024 年 13 卷 5 期

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收录情况： SCI

摘要： Simple Summary Crosstalk regulation is a common regulatory phenomenon in Streptomyces, typically mediated by regulatory factors within gene clusters. Utilizing these regulatory factors to enhance the production of target compounds represents an important approach. This study focuses on two regulatory factors, PteF and PteR, within the filipin gene cluster in Streptomyces avermitilis, investigating their effects on both avermectin production and overall cellular metabolism. The findings provide theoretical groundwork for constructing high-yielding engineered strains of avermectins and provide new insights into the role of PteF in the biosynthesis of avermectins and its impact on cellular metabolic processes. Crosstalk regulation is widespread in Streptomyces species. Elucidating the influence of a specific regulator on target biosynthetic gene clusters (BGCs) and cell metabolism is crucial for strain improvement through regulatory protein engineering. PteF and PteR are two regulators that control the biosynthesis of filipin, which competes for building blocks with avermectins in Streptomyces avermitilis. However, little is known about the effects of PteF and PteR on avermectin biosynthesis. In this study, we investigated their impact on avermectin biosynthesis and global cell metabolism. The deletion of pteF resulted in a 55.49% avermectin titer improvement, which was 23.08% higher than that observed from pteR deletion, suggesting that PteF plays a more significant role in regulating avermectin biosynthesis, while PteF hardly influences the transcription level of genes in avermectin and other polyketide BGCs. Transcriptome data revealed that PteF exhibited a global regulatory effect. Avermectin production enhancement could be attributed to the repression of the tricarboxylic acid cycle and fatty acid biosynthetic pathway, as well as the enhancement of pathways supplying acyl-CoA precursors. These findings provide new insights into the role of PteF on avermectin biosynthesis and cell metabolism, offering important clues for designing and building efficient metabolic pathways to develop high-yield avermectin-producing strains.

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