Activation of Secondary Metabolite Gene Clusters in Streptomyces clavuligerus by the PimM Regulator of Streptomyces natalensis

[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...

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Bibliographic Details
Authors: Martínez Burgo, Yolanda, Santos Aberturas, Javier, Rodríguez García, Antonio, García Barreales, Eva, Tormo, José Rubén, Truman, Andrew W., Reyes, Fernando, Aparicio Fernández, Jesús Manuel, Liras Padín, Paloma
Format: article
Status:Published version
Publication Date:2019
Country:España
Institution:Universidad Rey Juan Carlos
Repository:BULERIA. Repositorio Institucional de la Universidad de León
OAI Identifier:oai:buleria.unileon.es:10612/18075
Online Access:https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.00580/full
https://hdl.handle.net/10612/18075
Access Level:Open access
Keyword:Biotecnología
Streptomyces clavuligerus
Antibotics biosynthesis regulation
PimM
Clavulanic acid
Cephamycin C
Transcriptomics
2414.01 Antibióticos
2415.01 Biología Molecular de Microorganismos
Description
Summary:[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

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