Open AccessCrosstalk between ROS Homeostasis and Secondary Metabolism in S. natalensis ATCC 27448: Modulation of Pimaricin Production by Intracellular ROS
Author(s) -
Tiago Beites,
Sílvia Pires,
Catarina L. Santos,
Hugo Osório,
Pedro MoradasFerreira,
Marta V. Mendes
Publication year - 2011
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0027472
Subject(s) - intracellular , reactive oxygen species , microbiology and biotechnology , mutant , crosstalk , superoxide dismutase , catalase , metabolism , biochemistry , biology , secondary metabolism , homeostasis , chemistry , oxidative stress , enzyme , biosynthesis , gene , physics , optics
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 .