High level of antibiotic production in a double polyphosphate kinase and phosphate-binding protein mutant of Streptomyces lividans

Authors

  • Margarita Díaz,

    1. Instituto de Biología Funcional y Genómica/Departamento de Microbiología y Genética, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad de Salamanca, Salamanca, Spain
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  • Laura Sevillano,

    1. Instituto de Biología Funcional y Genómica/Departamento de Microbiología y Genética, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad de Salamanca, Salamanca, Spain
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  • Sergio Rico,

    1. Instituto de Biología Funcional y Genómica/Departamento de Microbiología y Genética, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad de Salamanca, Salamanca, Spain
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  • Felipe Lombo,

    1. Area de Microbiología, Departamento de Biología Funcional, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo, Spain
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  • Alfredo F. Braña,

    1. Area de Microbiología, Departamento de Biología Funcional, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo, Spain
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  • Jose A. Salas,

    1. Area de Microbiología, Departamento de Biología Funcional, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo, Spain
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  • Carmen Mendez,

    1. Area de Microbiología, Departamento de Biología Funcional, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo, Spain
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  • Ramón I. Santamaría

    Corresponding author
    • Instituto de Biología Funcional y Genómica/Departamento de Microbiología y Genética, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad de Salamanca, Salamanca, Spain
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Correspondence: Ramón I. Santamaría, Instituto de Biología Funcional y Genómica, Zacarías González sn, E-37007 Salamanca, Spain. Tel.: +34 923 294899; fax: +34 923 224876; e-mail: santa@usal.es

Abstract

Phosphate metabolism regulates most of the life processes of microorganisms. In the present work we obtained and studied a Streptomyces lividans ppk/pstS double mutant, which lacks polyphosphate kinase (PPK) and the high-affinity phosphate-binding protein (PstS), impairing at the same time the intracellular storage of polyphosphate and the intake of new inorganic phosphate from a phosphate-limited medium, respectively. In some of the aspects analyzed, the ppk/pstS double mutant was more similar to the wt strain than was the single pstS mutant. The double mutant was thus able to grow in phosphate-limited media, whereas the pstS mutant required the addition of 1 mM phosphate under the assay conditions used. The double mutant was able to incorporate more than one fourth of the inorganic phosphate incorporated by the wt strain, whereas phosphate incorporation was almost completely impaired in the pstS mutant. Noteworthy, under phosphate limitation conditions, the double ppk/pstS mutant showed a higher production of the endogenous antibiotic actinorhodin and the heterologous antitumor 8-demethyl-tetracenomycin (up to 10-fold with respect to the wt strain), opening new possibilities for the use of this strain in the heterologous expression of antibiotic pathways.

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