Activation and silencing of secondary metabolites in Streptomyces albus and Streptomyces lividans after transformation w
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Original Paper
Activation and silencing of secondary metabolites in Streptomyces albus and Streptomyces lividans after transformation with cosmids containing the thienamycin gene cluster from Streptomyces cattleya Alfredo F. Braña · Miriam Rodríguez · Pallab Pahari · Jurgen Rohr · Luis A. García · Gloria Blanco
Received: 21 August 2013 / Revised: 17 February 2014 / Accepted: 4 March 2014 / Published online: 15 March 2014 © Springer-Verlag Berlin Heidelberg 2014
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. Communicated by Erko Stackebrandt. Electronic supplementary material The online version of this article (doi:10.1007/s00203-014-0977-z) contains supplementary material, which is available to authorized users. A. F. Braña · M. Rodríguez · G. Blanco (*) Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, 33006 Oviedo, Spain e-mail: [email protected] P. Pahari · J. Rohr Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA L. A. García Departamento de Ingeniería Química y Tecnología del Medio Ambiente, Universidad de Oviedo, Oviedo, Spain
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. Keywords Antibiotic · Biosynthesis · Paulomycin · Paulomenol · Pyrazines · Tetramethyl-pyrazine · Dihydrobeta-agarofuran · Beta-patchoulene
Introduction Species of the Streptomyces genus are the main producers in nature of antibiotics and other bioactive secondary metabolites of great medical and industrial signific
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