RT info:eu-repo/semantics/article T1 Activation of Secondary Metabolite Gene Clusters in Streptomyces clavuligerus by the PimM Regulator of Streptomyces natalensis A1 Martínez Burgo, Yolanda A1 Santos Aberturas, Javier A1 Rodríguez García, Antonio A1 García Barreales, Eva A1 Tormo, José Rubén A1 Truman, Andrew W. A1 Reyes, Fernando A1 Aparicio Fernández, Jesús Manuel A1 Liras Padín, Paloma A2 Microbiologia K1 Biotecnología K1 Streptomyces clavuligerus K1 Antibotics biosynthesis regulation K1 PimM K1 Clavulanic acid K1 Cephamycin C K1 Transcriptomics K1 2414.01 Antibióticos K1 2415.01 Biología Molecular de Microorganismos AB [EN] Expression of non-native transcriptional activators may be a powerful general method to activate secondary metabolites biosynthetic pathways. PAS-LuxR regulators, whose archetype is PimM, activate the biosynthesis of polyene macrolide antifungals and other antibiotics, and have been shown to be functionally preserved across multiple Streptomyces strains. In this work we show that constitutive expression of pimM in Streptomyces clavuligerus ATCC 27064 significantly affected its transcriptome and modifies secondary metabolism. Almost all genes in three secondary metabolite clusters were overexpressed, including the clusters responsible for the biosynthesis of the clinically important clavulanic acid and cephamycin C. In comparison to a control strain, this resulted in 10- and 7-fold higher production levels of these metabolites, respectively. Metabolomic and bioactivity studies of S. clavuligerus::pimM also revealed deep metabolic changes. Antifungal activity absent in the control strain was detected in S. clavuligerus::pimM, and determined to be the result of a fivefold increase in the production of the tunicamycin complex PB Frontiers Media SA LK https://hdl.handle.net/10612/18075 UL https://hdl.handle.net/10612/18075 NO Martínez-Burgo, Y., Santos-Aberturas, J., Rodríguez-García, A., Barreales, E. G., Tormo, J. R., Truman, A. W., Reyes, F., Aparicio, J. F., & Liras, P. (2019). Activation of secondary metabolite gene clusters in Streptomyces clavuligerus by the PimM regulator of Streptomyces natalensis. Frontiers in microbiology, 10, Article e580. https://doi.org/10.3389/fmicb.2019.00580 DS BULERIA. Repositorio Institucional de la Universidad de León RD 20-may-2024