ArticleProtein science : a publication of the Protein Society2023
Degradation mechanism of AtrA mediated by ClpXP and its application in daptomycin production in Streptomyces roseosporus.
Article in Protein science : a publication of the Protein Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 4 citations in OpenAlex.
- Systematic Engineering of Proteases in Saccharopolyspora Spinosa Reveals Synergistic Enhancement of Spinosad Biosynthesis via Substrate Flux Optimization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Degradation mechanism of AtrA mediated by ClpXP and its application in daptomycin production in Streptomyces roseosporus.Protein science : a publication of the Protein Society · 2023Article
- Development of a native-locus dual reporter system for the efficient screening of the hyper-production of natural products inFrontiers in bioengineering and biotechnology · 2023Article
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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