Streptomyces tsukubaensis as a new model for carbon repression: transcriptomic response to tacrolimus repressing carbon sources

• Published in: Applied microbiology and biotechnology Vol. 101; no. 22; pp. 8181 - 8195
• Main Authors: Ordóñez-Robles, María, Santos-Beneit, Fernando, Albillos, Silvia M., Liras, Paloma, Martín, Juan F., Rodríguez-García, Antonio
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2017; Springer; Springer Nature B.V
• Subjects: Bacteria; Biomedical and Life Sciences; Biosynthetic Pathways - genetics; Biotechnology; Carbon; Carbon - metabolism; Carbon sources; Chemical properties; DNA microarrays; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Genes; Genomes; Genomics; Glucose; Glucose - metabolism; Glucose - pharmacology; Glycerol; Glycerol - metabolism; Glycerol - pharmacology; Life Sciences; Microarray Analysis; Microbial Genetics and Genomics; Microbiology; Physiological aspects; Proteomics; Streptomyces; Streptomyces - drug effects; Streptomyces - genetics; Streptomyces - growth & development; Streptomyces - metabolism; Streptomyces coelicolor - genetics; Tacrolimus; Transcription activation; Transcription factors; Transcriptome; Transcriptomics; FK506; Tacrolimus; Transcriptomics; Carbon regulation; Streptomyces tsukubaensis
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-017-8545-5

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.