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Arch Microbiol

Title:		Activation and silencing of secondary metabolites in Streptomyces albus and Streptomyces lividans after transformation with cosmids containing the thienamycin gene cluster from Streptomyces cattleya
Author(s):		Brana AF; Rodriguez M; Pahari P; Rohr J; Garcia LA; Blanco G;
Address:		"Departamento de Biologia Funcional e Instituto Universitario de Oncologia del Principado de Asturias, Universidad de Oviedo, 33006, Oviedo, Spain"
Journal Title:		Arch Microbiol
Year:		2014
Volume:		20140315
Issue:		5
Page Number:		345 - 355
DOI:		10.1007/s00203-014-0977-z
ISSN/ISBN:		1432-072X (Electronic) 0302-8933 (Linking)
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-beta-agarofuran and of interest in perfume industry as beta-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:		Anti-Bacterial Agents/*biosynthesis/chemistry Cosmids Gene Silencing Molecular Structure *Multigene Family Secondary Metabolism/*genetics Streptomyces/genetics/*metabolism Streptomyces lividans/genetics/*metabolism Thienamycins/biosynthesis Transformation;
Notes:		"MedlineBrana, Alfredo F Rodriguez, Miriam Pahari, Pallab Rohr, Jurgen Garcia, Luis A Blanco, Gloria eng Germany 2014/03/19 Arch Microbiol. 2014 May; 196(5):345-55. doi: 10.1007/s00203-014-0977-z. Epub 2014 Mar 15"