数字农科院2.0

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

文献类型： 外文期刊

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

作者机构：

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

期刊名称： Biology

ISSN： 2079-7737

年卷期： 2024 年 13 卷 5 期

页码：

收录情况： SCIE（2024版）

摘要： 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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