title: Crosstalk between ROS homeostasis and secondary metabolism in S. natalensis ATCC 27448: modulation of pimaricin production by intracellular ROS.
abstract: Streptomyces secondary metabolism is strongly affected by oxygen availability. The increased culture aeration enhances pimaricin production in S. natalensis, however the excess of O(2) consumption can lead to an intracellular ROS imbalance that is harmful to the cell. The adaptive physiological response of S. natalensis upon the addition of exogenous H(2)O(2) suggested that the modulation of the intracellular ROS levels, through the activation of the H(2)O(2) inducible catalase during the late exponential growth phase, can alter the production of pimaricin. With the construction of defective mutants on the H(2)O(2) related enzymes SodF, AhpCD and KatA1, an effective and enduring modulation of intracellular ROS was achieved. Characterization of the knock-out strains revealed different behaviours regarding pimaricin production: whilst the superoxide dismutase defective mutant presented low levels of pimaricin production compared to the wild-type, the mutants defective on the H(2)O(2)-detoxifying enzymes displayed a pimaricin overproducer phenotype. Using physiological and molecular approaches we report a crosstalk between oxidative stress and secondary metabolism regulatory networks. Our results reveal that the redox-based regulation network triggered by an imbalance of the intracellular ROS homeostasis is also able to modulate the biosynthesis of pimaricin in S. natalensis.
authors: Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors: Tiago
authors: T
authors: Beites
authors: Sílvia D S
authors: SD
authors: Pires
authors: Catarina L
authors: CL
authors: Santos
authors: Hugo
authors: H
authors: Osório
authors: Pedro
authors: P
authors: Moradas-Ferreira
authors: Marta V
authors: MV
authors: Mendes
mesh_terms: D002374:Catalase / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D006706:Homeostasis; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010866:Natamycin / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013302:Streptomyces / Q000187:drug effects* / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D016877:Oxidants; D017382:Reactive Oxygen Species; D010866:Natamycin; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase