Skip to main content
Log in

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

  • Genomics, transcriptomics, proteomics
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Angell S, Schwarz E, Bibb MJ (1992) The glucose kinase gene of Streptomyces coelicolor A3(2): its nucleotide sequence, transcriptional analysis and role in glucose repression. Mol Microbiol 6(19):2833–2844

    Article  CAS  PubMed  Google Scholar 

  • Arabolaza A, D'Angelo M, Comba S, Gramajo H (2010) FasR, a novel class of transcriptional regulator, governs the activation of fatty acid biosynthesis genes in Streptomyces coelicolor. Mol Microbiol 78(1):47–63

    CAS  PubMed  Google Scholar 

  • Ban YH, Park SR, Yoon YJ (2016) The biosynthetic pathway of FK506 and its engineering: from past achievements to future prospects. J Ind Microbiol Biotechnol 43(2–3):389–400

    Article  CAS  PubMed  Google Scholar 

  • Barreiro C, Martínez-Castro M (2014) Trends in the biosynthesis and production of the immunosuppressant tacrolimus (FK506). Appl Microbiol Biotechnol 98(2):497–507

    Article  CAS  PubMed  Google Scholar 

  • Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 57(1):289–300

    Google Scholar 

  • Blencke HM, Homuth G, Ludwig H, Mäder U, Hecker M, Stülke J (2003) Transcriptional profiling of gene expression in response to glucose in Bacillus subtilis: regulation of the central metabolic pathways. Metab Eng 5(2):133–149

    Article  CAS  PubMed  Google Scholar 

  • Breuder T, Hemenway CS, Movva NR, Cardenas ME, Heitman J (1994) Calcineurin is essential in cyclosporin A- and FK506-sensitive yeast strains. Proc Natl Acad Sci U S A 91(12):5372–5376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bucca G, Brassington AME, Hotchkiss G, Mersinias V, Smith CP (2003) Negative feedback regulation of dnaK, clpB and lon expression by the DnaK chaperone machine in Streptomyces coelicolor, identified by transcriptome and in vivo DnaK-depletion analysis. Mol Microbiol 50(1):153–166

    Article  CAS  PubMed  Google Scholar 

  • Bucca G, Laing E, Mersinias V, Allenby N, Hurd D, Holdstock J, Brenner V, Harrison M, Smith CP (2009) Development and application of versatile high density microarrays for genome-wide analysis of Streptomyces coelicolor: characterization of the HspR regulon. Genome Biol 10(1):R5

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen D, Zhang Q, Zhang Q, Cen P, Xu Z, Liu W (2012) Improvement of FK506 production in Streptomyces tsukubaensis by genetic enhancement of the supply of unusual polyketide extender units via utilization of two distinct site-specific recombination systems. Appl Environ Microbiol 78(15):5093–5103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Conesa A, Nueda MJ, Ferrer A, Talón M (2006) maSigPro: a method to identify significantly differential expression profiles in time-course microarray experiments. Bioinformatics 22(9):1096–1102

    Article  CAS  PubMed  Google Scholar 

  • Davis NK, Chater KF (1990) Spore colour in Streptomyces coelicolor A3(2) involves the developmentally regulated synthesis of a compound biosynthetically related to polyketide antibiotics. Mol Microbiol 4(10):1679–1691

    Article  CAS  PubMed  Google Scholar 

  • De León P, Marco S, Isiegas C, Marina A, Carrascosa JL, Mellado RP (1997) Streptomyces lividans groES, groEL1 and groEL2 genes. Microbiology 143(Pt 11):3563–3571

    Article  PubMed  Google Scholar 

  • De Mot R, Schoofs G, Nagy I (2007) Proteome analysis of Streptomyces coelicolor mutants affected in the proteasome system reveals changes in stress-responsive proteins. Arch Microbiol 188(3):257–271

    Article  PubMed  Google Scholar 

  • Díaz M, Esteban A, Fernández-Abalos JM, Santamaría RI (2005) The high-affinity phosphate-binding protein PstS is accumulated under high fructose concentrations and mutation of the corresponding gene affects differentiation in Streptomyces lividans. Microbiology 151(Pt 8):2583–2592

    Article  PubMed  Google Scholar 

  • Dominy JE Jr, Simmons CR, Karplus PA, Gehring AM, Stipanuk MH (2006) Identification and characterization of bacterial cysteine dioxygenases: a new route of cysteine degradation for eubacteria. J Bacteriol 188(15):5561–5569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du W, Huang D, Xia M, Wen J, Huang M (2014) Improved FK506 production by the precursors and product-tolerant mutant of Streptomyces tsukubaensis based on genome shuffling and dynamic fed-batch strategies. J Ind Microbiol Biotechnol 41(7):1131–1143

    Article  CAS  PubMed  Google Scholar 

  • Dufour YS, Wesenberg GE, Tritt AJ, Glasner JD, Perna NT, Mitchell JC, Donohue TJ (2010) chipD: a web tool to design oligonucleotide probes for high-density tiling arrays. Nucleic Acids Res 38(Web Server issue):W321–W325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Edgar R, Domrachev M, Lash AE (2002) Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30(1):207–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fink D, Weissschuh N, Reuther J, Wohlleben W, Engels A (2002) Two transcriptional regulators GlnR and GlnRII are involved in regulation of nitrogen metabolism in Streptomyces coelicolor A3(2). Mol Microbiol 46(2):331–347

    Article  CAS  PubMed  Google Scholar 

  • Fischer M, Schmidt C, Falke D, Sawers RG (2012) Terminal reduction reactions of nitrate and sulfate assimilation in Streptomyces coelicolor A3(2): identification of genes encoding nitrite and sulfite reductases. Res Microbiol 163(5):340–348

    Article  CAS  PubMed  Google Scholar 

  • Fowler-Goldsworthy K, Gust B, Mouz S, Chandra G, Findlay KC, Chater KF (2011) The actinobacteria-specific gene wblA controls major developmental transitions in Streptomyces coelicolor A3(2). Microbiology 157(Pt 5):1312–1328

    Article  CAS  PubMed  Google Scholar 

  • Gao C, Hindra, Mulder D, Yin C, Elliot MA (2012) Crp is a global regulator of antibiotic production in Streptomyces. mBio 3(6):e00407-e00412

  • González-Flecha B, Demple B (1995) Metabolic sources of hydrogen peroxide in aerobically growing Escherichia coli. J Biol Chem 270(23):13681–13687

    Article  PubMed  Google Scholar 

  • Gubbens J, Janus M, Florea BI, Overkleeft HS, van Wezel GP (2012) Identification of glucose kinase-dependent and -independent pathways for carbon control of primary metabolism, development and antibiotic production in Streptomyces coelicolor by quantitative proteomics. Mol Microbiol 86(6):1490–1507

    Article  CAS  PubMed  Google Scholar 

  • Gubbens J, Janus MM, Florea BI, Overkleeft HS, van Wezel GP (2017) Identification of glucose kinase-dependent and -independent pathways for carbon control of primary metabolism, development and antibiotic production in Streptomyces coelicolor by quantitative proteomics

  • Hahn JS, Oh SY, Roe JH (2002) Role of OxyR as a peroxide-sensing positive regulator in Streptomyces coelicolor A3(2). J Bacteriol 184(19):5214–5222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han L, Lobo S, Reynolds KA (1998) Characterization of β-ketoacyl-acyl carrier protein synthase III from Streptomyces glaucescens and its role in initiation of fatty acid biosynthesis. J Bacteriol 180(17):4481–4486

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hartl FU (1996) Molecular chaperones in cellular protein folding. Nature 381(6583):571–579

    Article  CAS  PubMed  Google Scholar 

  • Hopwood DA (2007) Streptomyces in nature and medicine: the antibiotic makers. Oxford University Press, New York

    Google Scholar 

  • Hurtubise Y, Shareck F, Kluepfel D, Morosoli R (1995) A cellulase/xylanase-negative mutant of Streptomyces lividans 1326 defective in cellobiose and xylobiose uptake is mutated in a gene encoding a protein homologous to ATP-binding proteins. Mol Microbiol 17(2):367–377

    Article  CAS  PubMed  Google Scholar 

  • Kallifidas D, Thomas D, Doughty P, Paget MSB (2010) The sigmaR regulon of Streptomyces coelicolor A3(2) reveals a key role in protein quality control during disulphide stress. Microbiology 156(Pt 6):1661–1672

    Article  CAS  PubMed  Google Scholar 

  • Kang SH, Huang J, Lee HN, Hur YA, Cohen SN, Kim ES (2007) Interspecies DNA microarray analysis identifies WblA as a pleiotropic down-regulator of antibiotic biosynthesis in Streptomyces. J Bacteriol 189(11):4315–4319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawamoto S, Watanabe M, Saito N, Hesketh A, Vachalova K, Matsubara K, Ochi K (2001) Molecular and functional analyses of the gene (eshA) encoding the 52-kilodalton protein of Streptomyces coelicolor A3(2) required for antibiotic production. J Bacteriol 183(20):6009–6016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keijser BJF, van Wezel GP, Canters GW, Vijgenboom E (2002) Developmental regulation of the Streptomyces lividans ram genes: involvement of RamR in regulation of the ramCSAB operon. J Bacteriol 184(16):4420–4429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim JS, Lee HN, Kim P, Lee HS, Kim ES (2012) Negative role of wblA in response to oxidative stress in Streptomyces coelicolor. J Microbiol Biotechnol 22(6):736–741

    Article  CAS  PubMed  Google Scholar 

  • Kim YJ, Moon MH, Song JY, Smith CP, Hong SK, Chang YK (2008) Acidic pH shock induces the expressions of a wide range of stress-response genes. BMC Genomics 9:604

    Article  PubMed  PubMed Central  Google Scholar 

  • Kino T, Hatanaka H, Hashimoto M, Nishiyama M, Goto T, Okuhara M, Kohsaka M, Aoki H, Imanaka H (1987a) FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. J Antibiot (Tokyo) 40(9):1249–1255

    Article  CAS  Google Scholar 

  • Kino T, Hatanaka H, Miyata S, Inamura N, Nishiyama M, Yajima T, Goto T, Okuhara M, Kohsaka M, Aoki H (1987b) FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. J Antibiot (Tokyo) 40(9):1256–1265

    Article  CAS  Google Scholar 

  • Kint C, Verstraeten N, Hofkens J, Fauvart M, Michiels J (2014) Bacterial Obg proteins: GTPases at the nexus of protein and DNA synthesis. Crit Rev Microbiol 40(3):207–224

    Article  CAS  PubMed  Google Scholar 

  • Kormanec J, Farkasovský M (1993) Differential expression of principal sigma factor homologues of Streptomyces aureofaciens correlates with the developmental stage. Nucleic Acids Res 21(16):3647–3652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lanzetta PA, Alvarez LJ, Reinach PS, Candia OA (1979) An improved assay for nanomole amounts of inorganic phosphate. Anal Biochem 100(1):95–97

    Article  CAS  PubMed  Google Scholar 

  • Lee K, Cohen SN (2003) A Streptomyces coelicolor functional orthologue of Escherichia coli RNase E shows shuffling of catalytic and PNPase-binding domains. Mol Microbiol 48(2):349–360

    Article  CAS  PubMed  Google Scholar 

  • Lodder J (1970) The yeasts, a taxonomic study. North Holland, Amsterdam, The Netherlands

    Google Scholar 

  • Lounès A, Lebrihi A, Benslimane C, Lefebvre G, Germain P (1996) Regulation of spiramycin synthesis in Streptomyces ambofaciens: effects of glucose and inorganic phosphate. Appl Microbiol Biotechnol 45(1–2):204–211

    Article  PubMed  Google Scholar 

  • Magasanik B (1961) Catabolite repression. Cold Spring Harb Symp Quant Biol 26:249–256

    Article  CAS  PubMed  Google Scholar 

  • Mao XM, Luo S, Zhou RC, Wang F, Yu P, Sun N, Chen XX, Tang Y, Li YQ (2015) Transcriptional regulation of the daptomycin gene cluster in Streptomyces roseosporus by an autoregulator, AtrA. J Biol Chem 290:7992–8001

    Article  CAS  PubMed  Google Scholar 

  • Martínez-Castro M, Salehi-Najafabadi Z, Romero F, Pérez-Sanchiz R, Fernández-Chimeno RI, Martín JF, Barreiro C (2013) Taxonomy and chemically semi-defined media for the analysis of the tacrolimus producer ‘Streptomyces tsukubaensis’. Appl Microbiol Biotechnol 97(5):2139–2152

    Article  PubMed  Google Scholar 

  • Mehra S, Lian W, Jayapal KP, Charaniya SP, Sherman DH, Hu WS (2006) A framework to analyze multiple time series data: a case study with Streptomyces coelicolor. J Ind Microbiol Biotechnol 33(2):159–172

    Article  CAS  PubMed  Google Scholar 

  • Mo S, Ban YH, Park JW, Yoo YJ, Yoon YJ (2009) Enhanced FK506 production in Streptomyces clavuligerus CKD1119 by engineering the supply of methylmalonyl-CoA precursor. J Ind Microbiol Biotechnol 36(12):1473–1482

    Article  CAS  PubMed  Google Scholar 

  • Mo S, Lee SK, Jin YY, Oh CH, Suh JW (2013) Application of a combined approach involving classical random mutagenesis and metabolic engineering to enhance FK506 production in Streptomyces sp. RM7011. Appl Microbiol Biotechnol 97(7):3053–3062

    Article  CAS  PubMed  Google Scholar 

  • Mo S, Lee SK, Jin YY, Suh JW (2016) Improvement of FK506 production in the high-yielding strain Streptomyces sp. RM7011 by engineering the supply of allylmalonyl-CoA through a combination of genetic and chemical approach. J Microbiol Biotechnol 26(2):233–240

    Article  CAS  PubMed  Google Scholar 

  • Nodwell JR, McGovern K, Losick R (1996) An oligopeptide permease responsible for the import of an extracellular signal governing aerial mycelium formation in Streptomyces coelicolor. Mol Microbiol 22(5):881–893

    Article  CAS  PubMed  Google Scholar 

  • Ordóñez-Robles M, Rodríguez-García A, Martín JF (2016) Target genes of the Streptomyces tsukubaensis FkbN regulator include most of the tacrolimus biosynthesis genes, a phosphopantetheinyl transferase and other PKS genes. Appl Microbiol Biotechnol 100(18):8091–8103

    Article  PubMed  Google Scholar 

  • Ohné M (1975) Regulation of the dicarboxylic acid part of the citric acid cycle in Bacillus subtilis. J Bacteriol 122(1):224–234

    PubMed  PubMed Central  Google Scholar 

  • Okamoto S, Ochi K (1998) An essential GTP-binding protein functions as a regulator for differentiation in Streptomyces coelicolor. Mol Microbiol 30(1):107–119

    Article  CAS  PubMed  Google Scholar 

  • Park HS, Shin SK, Yang YY, Kwon HJ, Suh JW (2005) Accumulation of S-adenosylmethionine induced oligopeptide transporters including BldK to regulate differentiation events in Streptomyces coelicolor M145. FEMS Microbiol Lett 249(2):199–206

    Article  CAS  PubMed  Google Scholar 

  • Park SJ, Gunsalus RP (1995) Oxygen, iron, carbon, and superoxide control of the fumarase fumA and fumC genes of Escherichia coli: role of the arcA, fnr, and soxR gene products. J Bacteriol 177(21):6255–6262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pérez-Redondo R, Santamarta I, Bovenberg R, Martín JF, Liras P (2010) The enigmatic lack of glucose utilization in Streptomyces clavuligerus is due to inefficient expression of the glucose permease gene. Microbiology 156(Pt 5):1527–1537

    Article  PubMed  Google Scholar 

  • Rabyk M, Ostash B, Rebets Y, Walker S, Fedorenko V (2011) Streptomyces ghanaensis pleiotropic regulatory gene wblA gh influences morphogenesis and moenomycin production. Biotechnol Lett 33(12):2481–2486

    Article  CAS  PubMed  Google Scholar 

  • Revill WP, Bibb MJ, Scheu AK, Kieser HJ, Hopwood DA (2001) β-Ketoacyl acyl carrier protein synthase III (FabH) is essential for fatty acid biosynthesis in Streptomyces coelicolor A3(2). J Bacteriol 183(11):3526–3530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rexer HU, Schäberle T, Wohlleben W, Engels A (2006) Investigation of the functional properties and regulation of three glutamine synthetase-like genes in Streptomyces coelicolor A3(2). Arch Microbiol 186(6):447–458

    Article  CAS  PubMed  Google Scholar 

  • Rodríguez E, Banchio C, Diacovich L, Bibb MJ, Gramajo H (2001) Role of an essential acyl coenzyme A carboxylase in the primary and secondary metabolism of Streptomyces coelicolor A3(2). Appl Environ Microbiol 67(9):4166–4176

    Article  PubMed  PubMed Central  Google Scholar 

  • Romero-Rodríguez A, Rocha D, Ruiz-Villafán B, Tierrafría V, Rodríguez-Sanoja R, Segura-González D, Sánchez S (2016a) Transcriptomic analysis of a classical model of carbon catabolite regulation in Streptomyces coelicolor. BMC Microbiol 16(1):77

    Article  PubMed  PubMed Central  Google Scholar 

  • Romero-Rodríguez A, Ruiz-Villafán B, Tierrafría V, Rodríguez-Sanoja R, Sánchez S (2016b) Carbon catabolite regulation of secondary metabolite formation and morphological differentiation in Streptomyces coelicolor. Appl Biochem Biotechnol 180(6):1152–1166

    Article  PubMed  Google Scholar 

  • Ruiz B, Chávez A, Forero A, García-Huante Y, Romero A, Sánchez M, Rocha D, Sánchez B, Rodríguez-Sanoja R, Sánchez S, Langley E (2010) Production of microbial secondary metabolites: regulation by the carbon source. Crit Rev Microbiol 36(2):146–167

    Article  CAS  PubMed  Google Scholar 

  • Saito N, Xu J, Hosaka T, Okamoto S, Aoki H, Bibb MJ, Ochi K (2006) EshA accentuates ppGpp accumulation and is conditionally required for antibiotic production in Streptomyces coelicolor A3(2). J Bacteriol 188(13):4952–4961

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saito A, Shinya T, Miyamoto K, Yokoyama T, Kaku H, Minami E, Shibuya N, Tsujibo H, Nagata Y, Ando A, Fujii T, Miyashita K (2007) The dasABC gene cluster, adjacent to dasR, encodes a novel ABC transporter for the uptake of N,N'-diacetylchitobiose in Streptomyces coelicolor A3(2). Appl Environ Microbiol 73(9):3000–3008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saito A, Fujii T, Shinya T, Shibuya N, Ando A, Miyashita K (2008) The msiK gene, encoding the ATPhydrolysing component of N,N′-diacetylchitobiose ABC transporters, is essential for induction of chitinase production in Streptomyces coelicolor A3(2). Microbiology 154(11):3358–3365 doi:10.1099/mic.0.2008/019612-0

  • Salehi-Najafabadi Z, Barreiro C, Rodríguez-García A, Cruz A, López GE, Martín JF (2014) The gamma-butyrolactone receptors BulR1 and BulR2 of Streptomyces tsukubaensis: tacrolimus (FK506) and butyrolactone synthetases production control. Appl Microbiol Biotechnol 98(11):4919–4936

    Article  CAS  PubMed  Google Scholar 

  • Sánchez S, Chávez A, Forero A, García-Huante Y, Romero A, Sánchez M, Rocha D, Sánchez B, Avalos M, Guzmán-Trampe S, Rodríguez-Sanoja R, Langley E, Ruiz B (2010) Carbon source regulation of antibiotic production. J Antibiot (Tokyo) 63(8):442–459

    Article  Google Scholar 

  • Santos-Beneit F, Rodríguez-García A, Apel AK, Martín JF (2009) Phosphate and carbon source regulation of two PhoP-dependent glycerophosphodiester phosphodiesterase genes of Streptomyces coelicolor. Microbiology 155(Pt 6):1800–1811

    Article  CAS  PubMed  Google Scholar 

  • Sidders B, Withers M, Kendall SL, Bacon J, Waddell SJ, Hinds J, Golby P, Movahedzadeh F, Cox RA, Frita R, Ten Bokum AMC, Wernisch L, Stoker NG (2007) Quantification of global transcription patterns in prokaryotes using spotted microarrays. Genome Biol 8(12):R265

    Article  PubMed  PubMed Central  Google Scholar 

  • Smith CP, Chater KF (1988) Structure and regulation of controlling sequences for the Streptomyces coelicolor glycerol operon. J Mol Biol 204(3):569–580

    Article  CAS  PubMed  Google Scholar 

  • Smyth GK (2004) Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3:3

    Article  Google Scholar 

  • Singh BP, Behera BK (2009) Regulation of tacrolimus production by altering primary source of carbons and amino acids. Lett Appl Microbiol 49(2):254–259

    Article  CAS  PubMed  Google Scholar 

  • Singh R, Reynolds KA (2015) Characterization of FabG and FabI of the Streptomyces coelicolor dissociated fatty acid synthase. Chembiochem 16(4):631–640

    Article  CAS  PubMed  Google Scholar 

  • Sola-Landa A, Rodríguez-García A, Apel AK, Martín JF (2008) Target genes and structure of the direct repeats in the DNA-binding sequences of the response regulator PhoP in Streptomyces coelicolor. Nucleic Acids Res 36(4):1358–1368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Solovyev V, Salamov A (2011) Automatic annotation of microbial genomes and metagenomic sequences. In: Li RW (ed) Metagenomics and its applications in agriculture, biomedicine and environmental studies. Nova Science, New York, pp 61–78

    Google Scholar 

  • Strakova E, Zikova A, Vohradsky J (2014) Inference of sigma factor controlled networks by using numerical modeling applied to microarray time series data of the germinating prokaryote. Nucleic Acids Res 42(2):748–763

    Article  CAS  PubMed  Google Scholar 

  • Swiatek MA, Gubbens J, Bucca G, Song E, Yang YH, Laing E, Kim BG, Smith CP, van Wezel GP (2013) The ROK family regulator Rok7B7 pleiotropically affects xylose utilization, carbon catabolite repression, and antibiotic production in Streptomyces coelicolor. J Bacteriol 195(6):1236–1248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Uguru GC, Stephens KE, Stead JA, Towle JE, Baumberg S, McDowall KJ (2005) Transcriptional activation of the pathway-specific regulator of the actinorhodin biosynthetic genes in Streptomyces coelicolor. Mol Microbiol 58(1):131–150

    Article  CAS  PubMed  Google Scholar 

  • van der Ploeg JR, Eichhorn E, Leisinger T (2001) Sulfonate-sulfur metabolism and its regulation in Escherichia coli. Arch Microbiol 176(1–2):1–8

    Article  PubMed  Google Scholar 

  • van Wezel GP, White J, Bibb MJ, Postma PW (1997a) The malEFG gene cluster of Streptomyces coelicolor A3(2): characterization, disruption and transcriptional analysis. Mol Gen Genet 254(5):604–608

    Article  PubMed  Google Scholar 

  • van Wezel GP, White J, Young P, Postma PW, Bibb MJ (1997b) Substrate induction and glucose repression of maltose utilization by Streptomyces coelicolor A3(2) is controlled by malR, a member of the lacl-galR family of regulatory genes. Mol Microbiol 23(3):537–549

    Article  PubMed  Google Scholar 

  • van Wezel GP, Mahr K, König M, Traag BA, Pimentel-Schmitt EF, Willimek A, Titgemeyer F (2005) GlcP constitutes the major glucose uptake system of Streptomyces coelicolor A3(2). Mol Microbiol 55(2):624–636

    Article  PubMed  Google Scholar 

  • van Wezel GP, McDowall KJ (2011) The regulation of the secondary metabolism of Streptomyces: new links and experimental advances. Nat Prod Rep 28(7):1311–1333

    Article  PubMed  Google Scholar 

  • Vemuri GN, Altman E, Sangurdekar DP, Khodursky AB, Eiteman MA (2006) Overflow metabolism in Escherichia coli during steady-state growth: transcriptional regulation and effect of the redox ratio. Appl Environ Microbiol 72(5):3653–3661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vujaklija D, Horinouchi S, Beppu T (1993) Detection of an A-factor-responsive protein that binds to the upstream activation sequence of strR, a regulatory gene for streptomycin biosynthesis in Streptomyces griseus. J Bacteriol 175(9):2652–2661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang CM, Cane DE (2008) Biochemistry and molecular genetics of the biosynthesis of the earthy odorant methylisoborneol in Streptomyces coelicolor. J Am Chem Soc 130(28):8908–8909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang YY, Zhang XS, Luo HD, Ren NN, Jiang XH, Jiang H, Li YQ (2016) Characterization of discrete phosphopantetheinyl transferases in Streptomyces tsukubaensis L19 unveils a complicate phosphopantetheinylation network. Sci Rep 6:24255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wanner BL (1993) Gene regulation by phosphate in enteric bacteria. J Cell Biochem 51(1):47–54

    Article  CAS  PubMed  Google Scholar 

  • Yoon YJ, Choi CY (1997) Nutrient effects on FK-506, a new immunosuppressant, production by Streptomyces sp. in a defined medium. J Ferment Bioeng 83(6):599–603

    Article  CAS  Google Scholar 

Download references

Acknowledgements

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).

Funding

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).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antonio Rodríguez-García.

Ethics declarations

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.

Electronic supplementary material

ESM 1

(PDF 1941 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ordóñez-Robles, M., Santos-Beneit, F., Albillos, S.M. et al. Streptomyces tsukubaensis as a new model for carbon repression: transcriptomic response to tacrolimus repressing carbon sources. Appl Microbiol Biotechnol 101, 8181–8195 (2017). https://doi.org/10.1007/s00253-017-8545-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-017-8545-5

Keywords

Navigation