The Onset of Tacrolimus Biosynthesis in Streptomyces tsukubaensis Is Dependent on the Intracellular Redox Status

The oxidative stress response is a key mechanism that microorganisms have to adapt to changeling environmental conditions. Adaptation is achieved by a fine-tuned molecular response that extends its influence to primary and secondary metabolism. In the past, the role of the intracellular redox status...

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Bibliographic Details
Published in:Antibiotics (Basel) 2020-10, Vol.9 (10), p.703
Main Authors: Pires, Sílvia D. S., Oliveira, Rute, Moradas-Ferreira, Pedro, V. Mendes, Marta
Format: Article
Language:English
Subjects:
Antioxidants
Availability
Biosynthesis
Carbon sources
Catalase
Cell growth
Chemical properties
Environmental conditions
Gene expression
Genetic engineering
Homeostasis
Hydrogen peroxide
Intracellular
Metabolic flux
Metabolism
Metabolites
Microorganisms
Observations
Oxidation
Oxidation-reduction reaction
Oxidative metabolism
Oxidative stress
Phenotypes
Physiological aspects
Precursors
Proteins
Proteomics
Scavenging
secondary metabolism
Strain
Streptomyces
Stress response
Tacrolimus
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Summary:The oxidative stress response is a key mechanism that microorganisms have to adapt to changeling environmental conditions. Adaptation is achieved by a fine-tuned molecular response that extends its influence to primary and secondary metabolism. In the past, the role of the intracellular redox status in the biosynthesis of tacrolimus in Streptomyces tsukubaensis has been briefly acknowledged. Here, we investigate the impact of the oxidative stress response on tacrolimus biosynthesis in S. tsukubaensis. Physiological characterization of S. tsukubaensis showed that the onset of tacrolimus biosynthesis coincided with the induction of catalase activity. In addition, tacrolimus displays antioxidant properties and thus a controlled redox environment would be beneficial for its biosynthesis. In addition, S. tsukubaensis ∆ahpC strain, a strain defective in the H2O2-scavenging enzyme AhpC, showed increased production of tacrolimus. Proteomic and transcriptomic studies revealed that the tacrolimus over-production phenotype was correlated with a metabolic rewiring leading to increased availability of tacrolimus biosynthetic precursors. Altogether, our results suggest that the carbon source, mainly used for cell growth, can trigger the production of tacrolimus by modulating the oxidative metabolism to favour a low oxidizing intracellular environment and redirecting the metabolic flux towards the increase availability of biosynthetic precursors.
ISSN:2079-6382
2079-6382
DOI:10.3390/antibiotics9100703