Insertional inactivation of mtrX and mtrY genes from the mithramycin gene cluster affects production and growth of the producer organism Streptomyces argillaceus

Authors

  • Jose Garcia-Bernardo,

    1. Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, 33006 Oviedo, Spain
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  • Alfredo F Braña,

    1. Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, 33006 Oviedo, Spain
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  • Carmen Méndez,

    1. Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, 33006 Oviedo, Spain
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  • José A Salas

    Corresponding author
    1. Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, 33006 Oviedo, Spain
      *Corresponding author. Tel./Fax: +34 (985) 103652, E-mail address: jasf@sauron.quimica.uniovi.es
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*Corresponding author. Tel./Fax: +34 (985) 103652, E-mail address: jasf@sauron.quimica.uniovi.es

Abstract

Mithramycin is an antitumor aromatic polyketide synthesized by Streptomyces argillaceus. Two genes (mtrX and mtrY) of the mithramycin gene cluster were inactivated by gene replacement. Inactivation of mtrX, that encodes an ABC excission nuclease system for DNA repair, produced a mutant that was affected in the normal rate of growth. Expression of mtrX in Streptomyces albus in a multicopy plasmid vector conferred a low increase in resistance to mithramycin. Inactivation of mtrY, that encodes a protein of unknown function, produced a 50% decrease in mithramycin biosynthesis. When mtrY was expressed in the wild-type S. argillaceus in a multicopy plasmid, this caused about 47% increase in the levels of mithramycin production. It is proposed that mtrX and mtrY could code for a secondary defense mechanism and a mithramycin regulatory element, respectively.

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