Lincomycin-Induced Secondary Metabolism in Streptomyces lividans 66 with a Mutation in the Gene Encoding the RNA Polymer
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Lincomycin‑Induced Secondary Metabolism in Streptomyces lividans 66 with a Mutation in the Gene Encoding the RNA Polymerase Beta Subunit Keiichiro Mukai1,2 · Momoko Kobayashi1,2 · Kanata Hoshino1,3 · Tomoko Maruyama1,2 · Daiki Hayashi4 · Ryoko Hamauzu1 · Takeshi Hosaka1,2,3,4 Received: 20 January 2020 / Accepted: 9 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Activating the genetic potential of Streptomyces strains to produce secondary metabolites can improve the production of useful biologically active compounds and facilitate the discovery of novel biologically active compounds. In this study, we found that Streptomyces lividans carrying the R440H mutation in rpoB, encoding the RNA polymerase beta subunit, grown in the presence of lincomycin at concentrations below the minimum inhibitory concentration (MIC) produced abundant amounts of actinorhodin and certain cryptic secondary metabolites despite culture conditions that restrict their production by the wild-type strain. The results indicate that lincomycin at concentrations below the MIC may strongly potentiate secondary metabolite production by Streptomyces strains carrying a specific rpoB mutation. In this study, we report an interesting phenomenon induced by combining the positive effects of certain rpoB mutations and concentration-dependent responses to lincomycin on secondary metabolism in S. lividans 66 and discuss the mechanisms and their applicability in exploring cryptic secondary metabolite production in streptomycetes.
Introduction Streptomycetes produce a wide variety of biologically active secondary metabolites, including antibiotics [1, 2]. Complete genomic sequence analyses revealed that gene clusters for the production of additional predicted secondary metabolites are carried by well-studied Streptomyces strains [3–6]. The exploitation and utilization of such genetic potential Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00284-020-02126-9) contains supplementary material, which is available to authorized users. * Takeshi Hosaka thosaka@shinshu‑u.ac.jp 1
Department of Biomolecular Innovation, Institute for Biomedical Sciences, Shinshu University, Nagano 399‑4598, Japan
2
Graduate School of Science and Technology, Shinshu University, Nagano 399‑4598, Japan
3
Graduate School of Medicine, Science and Technology, Shinshu University, Nagano 399‑4598, Japan
4
Faculty of Agriculture, Shinshu University, Nagano 399‑4598, Japan
in streptomycetes may therefore result in the discovery of novel biologically active compounds [7–9]. Our group has developed a method for potentiating secondary metabolite production by streptomycetes via certain mutations in rpoB encoding the RNA polymerase beta subunit [10–12]. Alternatively, we also found that the ribosome-targeting antibiotic lincomycin effectively induces the expression of genes involved in secondary metabolism in Streptomyces strains when added to culture medium at concentrations below the mini
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