Streptomyces tsukubaensis as a new model for carbon repression: transcriptomic response to tacrolimus repressing carbon sources
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In this work, we identified glucose and glycerol as tacrolimus repressing carbon sources in the important species Streptomyces tsukubaensis. A genome-wide analysis of the transcriptomic response to glucose and glycerol additions was performed using microarray technology. The transcriptional time series obtained allowed us to compare the transcriptomic profiling of S. tsukubaensis growing under tacrolimus producing and non-producing conditions. The analysis revealed important and different metabolic changes after the additions and a lack of transcriptional activation of the fkb cluster. In addition, we detected important differences in the transcriptional response to glucose between S. tsukubaensis and the model species Streptomyces coelicolor. A number of genes encoding key players of morphological and biochemical differentiation were strongly and permanently downregulated by the carbon sources. Finally, we identified several genes showing transcriptional profiles highly correlated to that of the tacrolimus biosynthetic pathway regulator FkbN that might be potential candidates for the improvement of tacrolimus production.
KeywordsStreptomyces tsukubaensis Tacrolimus FK506 Carbon regulation Transcriptomics
This work was supported by the European Union through an ERA-IB (PIM2010EEI-00677) international cooperation project. M. Ordóñez-Robles received a FPU fellowship of the Ministerio de Educación y Ciencia (Spain). We thank Dr. C. Prieto for sharing their prediction results of intrinsic terminators that were included in the microarray probe design. We acknowledge the technical support of B. Martín, J. Merino, A. Casenave and A. Mulero (INBIOTEC).
This study was funded by the Government of Spain (grant number PIM2010-EEI00677). María Ordóñez-Robles received a FPU grant from the Government of Spain (grant number AP2009-4508).
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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