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Activation and silencing of secondary metabolites in Streptomyces albus and Streptomyces lividans after transformation with cosmids containing the thienamycin gene cluster from Streptomyces cattleya

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Abstract

Activation and silencing of antibiotic production was achieved in Streptomyces albus J1074 and Streptomyces lividans TK21 after introduction of genes within the thienamycin cluster from S. cattleya. Dramatic phenotypic and metabolic changes, involving activation of multiple silent secondary metabolites and silencing of others normally produced, were found in recombinant strains harbouring the thienamycin cluster in comparison to the parental strains. In S. albus, ultra-performance liquid chromatography purification and NMR structural elucidation revealed the identity of four structurally related activated compounds: the antibiotics paulomycins A, B and the paulomenols A and B. Four volatile compounds whose biosynthesis was switched off were identified by gas chromatography–mass spectrometry analyses and databases comparison as pyrazines; including tetramethylpyrazine, a compound with important clinical applications to our knowledge never reported to be produced by Streptomyces. In addition, this work revealed the potential of S. albus to produce many others secondary metabolites normally obtained from plants, including compounds of medical relevance as dihydro-β-agarofuran and of interest in perfume industry as β-patchoulene, suggesting that it might be an alternative model for their industrial production. In S. lividans, actinorhodins production was strongly activated in the recombinant strains whereas undecylprodigiosins were significantly reduced. Activation of cryptic metabolites in Streptomyces species might represent an alternative approach for pharmaceutical drug discovery.

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Acknowledgments

This study was financial supported by the University of Oviedo (Ayuda Puente UNOV-10-MA-4). Thanks to Miguel Campoamor for his excellent GC–MS technical assistance. The authors are grateful to José L. Caso and José A. Guijarro for their continuous support. We also want to thank José A. Salas, Carmen Méndez and Luz E. Núñez for previous work on thienamycin.

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Authors and Affiliations

  1. Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, 33006, Oviedo, Spain

    Alfredo F. Braña, Miriam Rodríguez & Gloria Blanco

  2. Departamento de Ingeniería Química y Tecnología del Medio Ambiente, Universidad de Oviedo, Oviedo, Spain

    Luis A. García

  3. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA

    Pallab Pahari & Jurgen Rohr

Authors
  1. Alfredo F. Braña
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  2. Miriam Rodríguez
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  4. Jurgen Rohr
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  5. Luis A. García
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  6. Gloria Blanco
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Correspondence to Gloria Blanco.

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Communicated by Erko Stackebrandt.

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Braña, A.F., Rodríguez, M., Pahari, P. et al. Activation and silencing of secondary metabolites in Streptomyces albus and Streptomyces lividans after transformation with cosmids containing the thienamycin gene cluster from Streptomyces cattleya . Arch Microbiol 196, 345–355 (2014). https://doi.org/10.1007/s00203-014-0977-z

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