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• W4323531048 abstract "The efficiency of drug biosynthesis depends on different transcriptional regulatory pathways in Streptomyces, and the protein degradation system adds another layer of complexity to the regulatory processes. AtrA, a transcriptional regulator in the A-factor regulatory cascade, stimulates the production of daptomycin by binding to the dptE promoter in Streptomyces roseosporus. Using pull-down assays, bacterial two-hybrid system and knockout verification, we demonstrated that AtrA is a substrate for ClpP protease. Furthermore, we showed that ClpX is necessary for AtrA recognition and subsequent degradation. Bioinformatics analysis, truncating mutation, and overexpression proved that the AAA motifs of AtrA were essential for initial recognition in the degradation process. Finally, overexpression of mutated atrA (AAA-QQQ) in S. roseosporus increased the yield of daptomycin by 225% in shake flask and by 164% in the 15 L bioreactor. Thus, improving the stability of key regulators is an effective method to promote the ability of antibiotic synthesis." @default.
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• W4323531048 date "2023-03-22" @default.
• W4323531048 modified "2023-09-27" @default.
• W4323531048 title "Degradation mechanism of <scp>AtrA</scp> mediated by <scp>ClpXP</scp> and its application in daptomycin production in <i>Streptomyces roseosporus</i>" @default.
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• W4323531048 doi "https://doi.org/10.1002/pro.4617" @default.
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