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Transcriptional regulation of the fidaxomicin gene cluster and cellular development in YP-1 by the pleiotropic regulator MtrA. | LitMetric

AI Article Synopsis

  • Cascade regulation networks in microorganisms can be complex, particularly when trying to identify specific regulators for gene clusters.
  • This study used a method called "DNA to Proteins" affinity purification to identify MtrA, a global regulator that enhances fidaxomicin production by 37% when overexpressed.
  • By integrating the "Protein to DNAs" affinity purification technique (DAP-seq) with RNA-seq analysis, the research revealed MtrA's role in metabolic processes and offered new insights into improving fidaxomicin production while providing a fresh approach for studying cascade regulation networks.

Article Abstract

Cascade regulation networks are almost present in various kinds of microorganisms, but locating and systematically elucidating specific pleiotropic regulators related to a certain gene cluster can be a tricky problem. Here, based on the promoter of the fidaxomicin pathway-specific regulator FadR1, we utilized a "DNA to Proteins" affinity purification method and captured a global regulator MtrA, which positively regulates fidaxomicin biosynthesis. In the overexpressed strain, the production of fidaxomicin was improved by 37% compared to the native strain. Then, we combined the "Protein to DNAs" affinity purification method (DAP-seq) with the results of RNA-seq and systematically elucidated the primary and secondary metabolic processes in which MtrA directly or indirectly participates. Thus, our work brought up a new way to improve fidaxomicin production from the perspective of global regulation and analyzed the regulatory mechanism of MtrA. Meanwhile, we provided a novel methodology for the research of cascade regulation networks and vital secondary metabolites.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10714768PMC
http://dx.doi.org/10.1128/spectrum.02702-23DOI Listing

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