Antonie van Leeuwenhoek

, Volume 111, Issue 5, pp 761–781 | Cite as

Interplay between carbon, nitrogen and phosphate utilization in the control of secondary metabolite production in Streptomyces

  • Alba Romero-Rodríguez
  • Nidia Maldonado-Carmona
  • Beatriz Ruiz-Villafán
  • Niranjan Koirala
  • Diana Rocha
  • Sergio Sánchez


Streptomyces species are a wide and diverse source of many therapeutic agents (antimicrobials, antineoplastic and antioxidants, to name a few) and represent an important source of compounds with potential applications in medicine. The effect of nitrogen, phosphate and carbon on the production of secondary metabolites has long been observed, but it was not until recently that the molecular mechanisms on which these effects rely were ascertained. In addition to the specific macronutrient regulatory mechanisms, there is a complex network of interactions between these mechanisms influencing secondary metabolism. In this article, we review the recent advances in our understanding of the molecular mechanisms of regulation exerted by nitrogen, phosphate and carbon sources, as well as the effects of their interconnections, on the synthesis of secondary metabolites by members of the genus Streptomyces.


Secondary metabolism Antibiotic production Carbon regulation Regulation Streptomyces 



This work was supported by Grant CB-219686 from Consejo Nacional de Ciencia y Tecnología, Mexico.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants or animals

This article does not contain any studies with animals performed by any of the authors.


  1. Agarwal D, Gregory ST, O’Connor M (2011) Error-prone and error-restrictive mutations affecting ribosomal protein S12. J Mol Biol 410:1–9. PubMedCrossRefGoogle Scholar
  2. Allenby NEE, Laing E, Bucca G et al (2012) Diverse control of metabolism and other cellular processes in Streptomyces coelicolor by the PhoP transcription factor: genome-wide identification of in vivo targets. Nucleic Acids Res 40:9543–9556. PubMedPubMedCentralCrossRefGoogle Scholar
  3. Amin R, Franz-Wachtel M, Tiffert Y et al (2016) Post-translational serine/threonine phosphorylation and lysine acetylation: a novel regulatory aspect of the global nitrogen response regulator GlnR in S. coelicolor M145. Front Mol Biosci 3:1–14. CrossRefGoogle Scholar
  4. Angell S, Lewis CG, Buttner MJ, Bibb MJ (1994) Glucose repression in Streptomyces coelicolor A3(2): a likely regulatory role for glucose kinase. Mol Gen Genet 244:135–143PubMedCrossRefGoogle Scholar
  5. Baltz RH (2008) Renaissance in antibacterial discovery from actinomycetes. Curr Opin Pharmacol 8:557–563. PubMedCrossRefGoogle Scholar
  6. Běhal V, Hošťálek Z, Vaněk Z (1971) Anhydrotetracycline oxygenase activity and biosynthesis of tetracyclines in Streptomyces aureofaciens. Biotechnol Lett 1:177–182CrossRefGoogle Scholar
  7. Bérdy J (2012) Thoughts and facts about antibiotics: where we are now and where we are heading. J Antibiot 65:385–395. PubMedCrossRefGoogle Scholar
  8. Bertram R, Rigali S, Wood N et al (2011) Regulon of the N-acetylglucosamine utilization regulator NagR in Bacillus subtilis. J Bacteriol 193:3525–3536. PubMedPubMedCentralCrossRefGoogle Scholar
  9. Bibb MJ (2005) Regulation of secondary metabolism in streptomycetes. Curr Opin Microbiol 8:208–215. PubMedCrossRefGoogle Scholar
  10. Borodina I, Siebring J, Zhang J et al (2008) Antibiotic overproduction in Streptomyces coelicolor A3(2) mediated by phosphofructokinase deletion. J Biol Chem 283:25186–25199. PubMedCrossRefGoogle Scholar
  11. Butler MJ, Bruheim P, Jovetic S et al (2002) Engineering of primary carbon metabolism for improved antibiotic production in Streptomyces lividans. Appl Environ Microbiol 68:4731–4739. PubMedPubMedCentralCrossRefGoogle Scholar
  12. Challis GL, Hopwood DA (2003) Synergy and contingency as driving forces for the evolution of multiple secondary metabolite production by Streptomyces species. Proc Natl Acad Sci USA 100(Suppl):14555–14561. PubMedPubMedCentralCrossRefGoogle Scholar
  13. Chandra G, Pullan ST, Chandra G et al (2011) Genome-wide analysis of the role of GlnR in Streptomyces venezuelae provides new insights into global nitrogen regulation in actinomycetes. BMC Genom. 12:175. CrossRefGoogle Scholar
  14. Chater KF, Biró S, Lee KJ et al (2010) The complex extracellular biology of Streptomyces. FEMS Microbiol Rev 34:171–198. PubMedCrossRefGoogle Scholar
  15. Chaudhary AK, Dhakal D, Sohng JK (2013) An Insight into the -Omics; Based Engineering of Streptomycetes for Secondary Metabolite Overproduction. Biomed Res Int 2013:e968518. CrossRefGoogle Scholar
  16. Chávez A, García-Huante Y, Ruiz B et al (2009) Cloning and expression of the sco2127 gene from Streptomyces coelicolor M145. J Ind Microbiol Biotechnol 36:649–654. PubMedCrossRefGoogle Scholar
  17. Chávez A, Forero A, Sánchez M et al (2011) Interaction of SCO2127 with BldKB and its possible connection to carbon catabolite regulation of morphological differentiation in Streptomyces coelicolor. Appl Microbiol Biotechnol 89:799–806. PubMedCrossRefGoogle Scholar
  18. Colson S, Stephan J, Hertrich T et al (2007) Conserved cis-acting elements upstream of genes composing the chitinolytic system of streptomycetes are DasR-responsive elements. J Mol Microbiol Biotechnol 12:60–66. PubMedCrossRefGoogle Scholar
  19. Coze F, Gilard F, Tcherkez G et al (2013) Carbon-flux distribution within Streptomyces coelicolor metabolism: a comparison between the actinorhodin-producing strain M145 and its non-producing derivative M1146. PLoS ONE. PubMedPubMedCentralCrossRefGoogle Scholar
  20. Dahal B, NandaKafle G, Perkins L, Brözel VS (2017) Diversity of free-Living nitrogen fixing Streptomyces in soils of the badlands of South Dakota. Microbiol Res 195:31–39. PubMedCrossRefGoogle Scholar
  21. Demain AL (1989) Carbon source regulation of idiolite biosynthesis. In: Shapiro S (ed) Regulation of secondary metabolism of actinomycetes. CRC Press, Boca Raton, pp 127–134Google Scholar
  22. Demain AL, Sanchez S (2009) Microbial drug discovery: 80 years of progress. J Antibiot. PubMedCrossRefGoogle Scholar
  23. 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 151:2583–2592. PubMedCrossRefGoogle Scholar
  24. Dubeau MP, Poulin-Laprade D, Ghinet MG, Brzezinski R (2011) Properties of CsnR, the transcriptional repressor of the chitosanase gene, csnA, of Streptomyces lividans. J Bacteriol 193(10):2441–2450. PubMedPubMedCentralCrossRefGoogle Scholar
  25. Fang A, Demain AL (1995) Exogenous shikimic acid stimulates rapamycin biosynthesis in Streptomyces hygroscopicus. Folia Microbiol 40:607–610CrossRefGoogle Scholar
  26. Fischer M, Alderson J, Van Keulen G et al (2010) The obligate aerobe Streptomyces coelicolor A3(2) synthesizes three active respiratory nitrate reductases. Microbiology 156:3166–3179. PubMedCrossRefGoogle Scholar
  27. Forero A, Sánchez M, Chávez A et al (2012) Possible involvement of the sco2127 gene product in glucose repression of actinorhodin production in Streptomyces coelicolor. Can J Microbiol 58:1195–1201. PubMedCrossRefGoogle Scholar
  28. Gil J, Naharro G, Villanueva J, Martín JF (1985) Characterization and regulation of p-aminobenzoic acid synthase from Streptomyces griseus. J Gen Microbiol 131:1279–1287PubMedGoogle Scholar
  29. Görke B, Stülke J (2008) Carbon catabolite repression in bacteria: many ways to make the most out of nutrients. Nat Rev Microbiol 6:613–624. PubMedCrossRefGoogle Scholar
  30. Gubbens J, Janus M, Florea BI et al (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 6:1490–1507. CrossRefGoogle Scholar
  31. Guzman S, Carmona A, López R, Escalante L, Ruiz B, Rodríguez-Sanoja R, Sánchez S, Langley E (2005) Pleiotropic effect of the sco2127 gene on the glucose uptake, glucose kinase activity and carbon catabolite repression in Streptomyces peucetius var. caesius. Microbiology-SGM 151:1717–1723CrossRefGoogle Scholar
  32. Haiser HJ, Karginov FV, Hannon GJ, Elliot MA (2008) Developmentally regulated cleavage of tRNAs in the bacterium Streptomyces coelicolor. Nucleic Acids Res 36:732–741. PubMedCrossRefGoogle Scholar
  33. Harper CJ, Hayward D, Kidd M et al (2010) Glutamate dehydrogenase and glutamine synthetase are regulated in response to nitrogen availability in Myocbacterium smegmatis. BMC Microbiol 10:138. PubMedPubMedCentralCrossRefGoogle Scholar
  34. Hindle Z, Smith CP (1994) Substrate induction and catabolite repression of the Streptomyces coelicolor glycerol operon are mediated through the GylR protein. Mol Microbiol 12:737–745. PubMedCrossRefGoogle Scholar
  35. Hodgson DA (1982) Glucose repression of carbon source uptake and metabolism in Streptomyces coelicolor A3(2) and its perturbation in mutants resistant to 2-Deoxyglucose. J Gen Microbiol 128:2417–2430. CrossRefGoogle Scholar
  36. Hodgson DA (2000) Primary metabolism and its control in streptomycetes: a most unusual group of bacteria. Adv Microb Phys 42:47–238CrossRefGoogle Scholar
  37. Hwang KS, Kim HU, Charusanti P et al (2014) Systems biology and biotechnology of Streptomyces species for the production of secondary metabolites. Biotechnol Adv 32:255–268. PubMedCrossRefGoogle Scholar
  38. Jenkins VA, Barton GR, Robertson BD, Williams KJ (2013) Genome wide analysis of the complete GlnR nitrogen-response regulon in Mycobacterium smegmatis. BMC Genom. 14:301. CrossRefGoogle Scholar
  39. Kim J-N, Jeong Y, Yoo J et al (2015) Genome-scale analysis reveals a role for NdgR in the thiol oxidative stress response in Streptomyces coelicolor. BMC Genom. 16:116. CrossRefGoogle Scholar
  40. Krysenko S, Okoniewski N, Kulik A et al (2017) Gamma-glutamylpolyamine synthetase GlnA3 is involved in the first step of polyamine degradation pathway in Streptomyces coelicolor M145. Front Microbiol 8:1–18. CrossRefGoogle Scholar
  41. Kusano T, Suzuki H (eds) (2015) Polyamines a universal molecular nexus for growth, survival and specialized metabolism. Springer, BerlinGoogle Scholar
  42. Kwakman JH, Postma PW (1994) Glucose kinase has a regulatory role in carbon catabolite repression in Streptomyces coelicolor. J Bacteriol 176:2694–2698. PubMedPubMedCentralCrossRefGoogle Scholar
  43. Li R, Townsend CA (2006) Rational strain improvement for enhanced clavulanic acid production by genetic engineering of the glycolytic pathway in Streptomyces clavuligerus. Metab Eng 8:240–252. PubMedCrossRefGoogle Scholar
  44. Liao C, Yao L, Xu Y et al (2015) Nitrogen regulator GlnR controls uptake and utilization of non-phosphotransferase-system carbon sources in actinomycetes. Proc Natl Acad Sci 112:201508465. CrossRefGoogle Scholar
  45. Liu G, Chater KF, Chandra G et al (2013) Molecular regulation of antibiotic biosynthesis in streptomyces. Microbiol Mol Biol Rev 77:112–143. PubMedPubMedCentralCrossRefGoogle Scholar
  46. Mahr K, van Wezel GP, Svensson C et al (2001) Glucose kinase of Streptomyces coelicolor A3(2): large-scale purification and biochemical analysis. Antonie Van Leeuwenhoek 78:253–261CrossRefGoogle Scholar
  47. Martín JF (1989) Molecular mechanisms for the control by phosphate of the biosynthesis of antibiotic and secondary metabolism. In: Shapiro S (ed) Regulation of secondary metabolism of actinomycetes1. CRC Press, Boca Raton, pp 213–237Google Scholar
  48. Martín JF (2004) Phosphate control of the biosynthesis of antibiotics and other secondary metabolites is mediated by the PhoR-PhoP system: an unfinished story. J Bacteriol 186:5197–5201. PubMedPubMedCentralCrossRefGoogle Scholar
  49. Martin JF, Demain AL (1980) Control of antibiotic biosynthesis. Microbiol Rev 44:230–251PubMedPubMedCentralGoogle Scholar
  50. Martín JF, Sola-Landa A, Santos-beneit F et al (2011) Cross-talk of global nutritional regulators in the control of primary and secondary metabolism in Streptomyces. Microb Biotechnol 4:165–174. PubMedPubMedCentralCrossRefGoogle Scholar
  51. McCormick JR, Flärdh K (2012) Signals and regulators that govern Streptomyces development. FEMS Microbiol Rev 36:206–231. PubMedCrossRefGoogle Scholar
  52. Miller-Fleming L, Olin-Sandoval V, Campbell K, Ralser M (2015) Remaining mysteries of molecular biology: the role of polyamines in the cell. J Mol Biol 427:3389–3406. PubMedCrossRefGoogle Scholar
  53. Nazari B, Kobayashi M, Saito A et al (2013) Chitin-induced gene expression in secondary metabolic pathways of Streptomyces coelicolor A3(2) grown in soil. Appl Environ Microbiol 79:707–713. PubMedPubMedCentralCrossRefGoogle Scholar
  54. Nguyen QT, Merlo ME, Medema MH et al (2012) Metabolomics methods for the synthetic biology of secondary metabolism. FEBS Lett 586:2177–2183. PubMedCrossRefGoogle Scholar
  55. Nothaft H, Dresel D, Willimek A et al (2003) The phosphotransferase system of Streptomyces coelicolor is biased for N-acetylglucosamine metabolism. J Bacteriol 185:7019–7023. PubMedPubMedCentralCrossRefGoogle Scholar
  56. Nothaft H, Rigali S, Boomsma B et al (2010) The permease gene nagE2 is the key to N-acetylglucosamine sensing and utilization in Streptomyces coelicolor and is subject to multi-level control. Mol Microbiol 75:1133–1144. PubMedCrossRefGoogle Scholar
  57. Olano C, Lombó F, Méndez C, Salas JA (2008) Improving production of bioactive secondary metabolites in actinomycetes by metabolic engineering. Metab Eng 10:281–292. PubMedCrossRefGoogle Scholar
  58. Omura S, Tanaka Y, Mamada H, Masuma R (1984) Effect of ammonium ion, inorganic phosphate and amino acids on the biosynthesis of protylonolide, a precursor of tylosin aglycone. J Antibiot 37:494–502. PubMedCrossRefGoogle Scholar
  59. Omura S, Ikeda H, Ishikawa J et al (2001) Genome sequence of an industrial microorganism Streptomyces avermitilis: deducing the ability of producing secondary metabolites. Proc Natl Acad Sci 98:12215–12220. PubMedPubMedCentralCrossRefGoogle Scholar
  60. Ordóñez-Robles M, Martín JF, Santos-Beneit F, Rodríguez-garcía A (2017) Analysis of the Pho regulon in Streptomyces tsukubaensis. Microbiol Res 205:80–87. PubMedCrossRefGoogle Scholar
  61. Osbourn A (2010) Secondary metabolic gene clusters: evolutionary toolkits for chemical innovation. Trends Genet 26:449–457. PubMedCrossRefGoogle Scholar
  62. Papagianni M (2012) Recent advances in engineering the central carbon metabolism of industrially important bacteria. Microb Cell Fact 11:50. PubMedPubMedCentralCrossRefGoogle Scholar
  63. Pérez-Redondo R, Rodríguez-García A, Botas A et al (2012) ArgR of Streptomyces coelicolor is a versatile regulator. PLoS ONE. PubMedPubMedCentralCrossRefGoogle Scholar
  64. Piir K, Paier A, Liiv A et al (2011) Ribosome degradation in growing bacteria. EMBO Rep 12:458–462. PubMedPubMedCentralCrossRefGoogle Scholar
  65. Qu S, Kang Q, Wu H et al (2015) Positive and negative regulation of GlnR in validamycin A biosynthesis by binding to different loci in promoter region. Appl Microbiol Biotechnol 99:4771–4783. PubMedCrossRefGoogle Scholar
  66. Rao NN, Gómez-García MR, Kornberg A (2009) Inorganic polyphosphate: essential for growth and survival. Annu Rev Biochem 78:605–647. PubMedCrossRefGoogle Scholar
  67. Rigali S et al (2006) The sugar phosphotransferase system of Streptomyces coelicolor is regulated by the GntR-family regulator DasR and links N-acetylglucosamine metabolism to the control of development. Mol Microbiol 61:1237–1251. PubMedCrossRefGoogle Scholar
  68. Rigali S et al (2008) Feast or famine: the global regulator DasR links nutrient stress to antibiotic production by Streptomyces. EMBO Rep 9:670–675. PubMedPubMedCentralCrossRefGoogle Scholar
  69. Rodríguez-García A, Barreiro C, Santos-Beneit F et al (2007) Genome-wide transcriptomic and proteomic analysis of the primary response to phosphate limitation in Streptomyces coelicolor M145 and in a ΔphoP mutant. Proteomics 7:2410–2429. PubMedCrossRefGoogle Scholar
  70. Rodríguez-García A, Sola-Landa A, Apel K et al (2009) Phosphate control over nitrogen metabolism in Streptomyces coelicolor: direct and indirect negative control of glnR, glnA, glnII and amtB expression by the response regulator PhoP. Nucleic Acids Res 37:3230–3242. PubMedPubMedCentralCrossRefGoogle Scholar
  71. Rokem JS, Lantz AE, Nielsen J (2007) Systems biology of antibiotic production by microorganisms. Nat Prod Rep 24:1262. PubMedCrossRefGoogle Scholar
  72. Romero-Rodríguez A, Robledo-Casados I, Sánchez S (2015) An overview on transcriptional regulators in Streptomyces. Biochim Biophys Acta Gene Regul Mech 1849:1017–1039. CrossRefGoogle Scholar
  73. Romero-Rodríguez A, Rocha D, Ruiz-Villafan B et al (2016a) Transcriptomic analysis of a classical model of carbon catabolite regulation in Streptomyces coelicolor. BMC Microbiol. PubMedPubMedCentralCrossRefGoogle Scholar
  74. Romero-Rodríguez A, Ruiz-Villafán B, Tierrafría VH et al (2016b) Carbon Catabolite Regulation of Secondary Metabolite Formation and Morphological Differentiation in Streptomyces coelicolor. Appl Biochem Biotechnol. PubMedCrossRefGoogle Scholar
  75. Romero-Rodríguez A, Rocha D, Ruiz-Villafán B et al (2017) Carbon catabolite regulation in Streptomyces: new insights and lessons learned. World J Microbiol Biotechnol. PubMedCrossRefGoogle Scholar
  76. Ruiz B, Chávez A, Forero A et al (2010) Production of microbial secondary metabolites: regulation by the carbon source. Crit Rev Microbiol 36:146–167. PubMedCrossRefGoogle Scholar
  77. Ryu YG, Butler MJ, Chater KF, Lee KJ (2006) Engineering of primary carbohydrate metabolism for increased production of actinorhodin in Streptomyces coelicolor. Appl Environ Microbiol 72:7132–7139. PubMedPubMedCentralCrossRefGoogle Scholar
  78. Saito A, Shinya T, Miyamoto K et al (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 73:3000–3008. PubMedPubMedCentralCrossRefGoogle Scholar
  79. Santos-Beneit F (2015) The Pho regulon: a huge regulatory network in bacteria. Front Microbiol 6:1–13. CrossRefGoogle Scholar
  80. Santos-Beneit F, Rodríguez-García A, Sola-Landa A, Martín JF (2009) Cross-talk between two global regulators in Streptomyces: PhoP and AfsR interact in the control of afsS, pstS and phoRP transcription. Mol Microbiol 72:53–68. PubMedCrossRefGoogle Scholar
  81. Schniete JK, Cruz-Morales P, Selem-Mojica N et al (2018) Expanding primary metabolism helps generate the metabolic robustness to facilitate antibiotic biosynthesis in Streptomyces. MBio 9:e02283-17. PubMedPubMedCentralCrossRefGoogle Scholar
  82. Segura D, Rodríguez R, Sandoval T et al (1996) Streptomyces mutants insensitive to glucose repression showed deregulation of primary and secondary metabolism. Asia Pacific J Mol Biotechnol 4:30–36Google Scholar
  83. Seo J, Ohnishi Y, Hirata A, Horinouchi S (2002) ATP-binding cassette transport system involved in regulation of morphological differentiation in response to glucose in Streptomyces griseus. J Bacteriol 184:91–103. PubMedPubMedCentralCrossRefGoogle Scholar
  84. Shao ZH, Deng WX, Li SY et al (2015) GlnR-mediated regulation of ectABCD transcription expands the role of the GlnR regulon to osmotic stress management. J Bacteriol 197:3041–3047. PubMedPubMedCentralCrossRefGoogle Scholar
  85. Sharma UK, Chatterji D (2010) Transcriptional switching in Escherichia coli during stress and starvation by modulation of σ70 activity. FEMS Microbiol Rev 34:646–657. PubMedCrossRefGoogle Scholar
  86. Shu D, Chen L, Wang W et al (2009) afsQ1-Q2-sigQ is a pleiotropic but conditionally required signal transduction system for both secondary metabolism and morphological development in Streptomyces coelicolor. Appl Microbiol Biotechnol 81:1149–1160. PubMedCrossRefGoogle Scholar
  87. Smirnov A, Esnault C, Prigent M et al (2015) Phosphate homeostasis in conditions of phosphate proficiency and limitation in the wild type and the phoP mutant of Streptomyces lividans. PLoS ONE 10:1–14. CrossRefGoogle Scholar
  88. Smith CP, Chater KF (1988) Structure and regulation of controlling sequences for the Streptomyces coelicolor glycerol operon. J Mol Biol 204:569–580. PubMedCrossRefGoogle Scholar
  89. Sola-Landa A, Moura RS, Martín JF (2003) The two-component PhoR-PhoP system controls both primary metabolism and secondary metabolite biosynthesis in Streptomyces lividans. Proc Natl Acad Sci USA 100:6133–6138. PubMedPubMedCentralCrossRefGoogle Scholar
  90. Sola-Landa A, Rodríguez-García A, Franco-Domínguez E, Martín JF (2005) Binding of PhoP to promoters of phosphate-regulated genes in Streptomyces coelicolor: identification of PHO boxes. Mol Microbiol 56:1373–1385. PubMedCrossRefGoogle Scholar
  91. Sola-Landa A, Rodríguez-García A, Amin R et al (2013) Competition between the GlnR and PhoP regulators for the glnA and amtB promoters in Streptomyces coelicolor. Nucleic Acids Res 41:1767–1782. PubMedCrossRefGoogle Scholar
  92. Świątek MA, Gubbens J, Bucca G et al (2013) The ROK family regulator Rok7B7 pleiotropically affects xylose utilization, carbon catabolite repression, and antibiotic production in Streptomyces coelicolor. J Bacteriol 195:1236–1248. PubMedPubMedCentralCrossRefGoogle Scholar
  93. Świątek-Połatyńska MA, Bucca G, Laing E et al (2015) Genome-wide analysis of in vivo binding of the master regulator DasR in Streptomyces coelicolor identifies novel non-canonical targets. PLoS ONE 10:1–24. CrossRefGoogle Scholar
  94. Tenconi E, Jourdan S, Motte P et al (2012) Extracellular sugar phosphates are assimilated by Streptomyces in a PhoP-dependent manner. Antonie van Leeuwenhoek, Int J Gen Mol Microbiol 102:425–433. CrossRefGoogle Scholar
  95. Tenconi E, Traxler MF, Hoebreck C, van Wezel GP, Rigali S (2018) Prodiginine production in Streptomyces coelicolor correlates temporally and spatially to programmed cell death. bioRxiv preprint first posted online Jan 19, 2018.
  96. Tenconi E, Traxler M, Hoebreck C et al (2018b) Prodiginine production in Streptomyces coelicolor correlates temporally and spatially to programmed cell death. BioRXiv. CrossRefGoogle Scholar
  97. Tierrafría VH, Licona-Cassani C, Maldonado-Carmona N et al (2016) Deletion of the hypothetical protein SCO2127 of Streptomyces coelicolor allowed identification of a new regulator of actinorhodin production. Appl Microbiol Biotechnol 100:9229–9237CrossRefGoogle Scholar
  98. Tiffert Y, Supra P, Wurm R et al (2008) The Streptomyces coelicolor GlnR regulon: identification of new GlnR targets and evidence for a central role of GlnR in nitrogen metabolism in actinomycetes. Mol Microbiol 67:861–880. PubMedCrossRefGoogle Scholar
  99. Tiffert Y, Franz-wachtel M, Fladerer C et al (2011) Proteomic analysis of the GlnR-mediated response to nitrogen limitation in Streptomyces coelicolor M145. Appl Microbiol Biotechnol 89:1149–1159. PubMedCrossRefGoogle Scholar
  100. Titgemeyer F, Reizer J, Reizer A, Saier MH (1994) Evolutionary relationships between sugar kinases and transcriptional repressors in bacteria. Microbiology 140:2349–2354. PubMedCrossRefGoogle Scholar
  101. Traxler MF, Kolter R (2015) Natural products in soil microbe interactions and evolution. Nat Prod Rep 32:956–970. PubMedCrossRefGoogle Scholar
  102. Uguru GC, Stephens KE, Stead JA et al (2005) Transcriptional activation of the pathway-specific regulator of the actinorhodin biosynthetic genes in Streptomyces coelicolor. Mol Microbiol 58:131–150. PubMedCrossRefGoogle Scholar
  103. Urem M, Świątek-Połatyńska MA, Rigali S, van Wezel GP (2016) Intertwining nutrient-sensory networks and the control of antibiotic production in Streptomyces. Mol Microbiol 102:183–195. PubMedCrossRefGoogle Scholar
  104. van Keulen G, Dyson PJ (2014) Chapter six—production of specialized metabolites by Streptomyces coelicolor A3(2), 1st edn. Elsevier Inc., AmsterdamGoogle Scholar
  105. van Wezel GP, McDowall KJ (2011) The regulation of the secondary metabolism of Streptomyces: new links and experimental advances. Nat Prod Rep 28:1311. PubMedCrossRefGoogle Scholar
  106. van Wezel GP, Mahr K, König M et al (2005) GlcP constitutes the major glucose of uptake system of Streptomyces coelicolor A3(2). Mol Microbiol 55:624–636. PubMedCrossRefGoogle Scholar
  107. van Wezel GP, König M, Mahr K et al (2007) A new piece of an old jigsaw: glucose kinase is activated posttranslationally in a glucose transport-dependent manner in Streptomyces coelicolor A3(2). J Mol Microbiol Biotechnol 12:67–74. PubMedCrossRefGoogle Scholar
  108. Vu-Trong K, Bhuwapathanapun S, Gray PP (1981) Metabolic regulation in tylosin-producing Streptomyces fradiae: phosphate control of tylosin biosynthesis. Antimicrob Agents Chemother 19:209–212. PubMedPubMedCentralCrossRefGoogle Scholar
  109. Wang J, Zhao GP (2009) GlnR positively regulates nasA transcription in Streptomyces coelicolor. Biochem Biophys Res Commun 386:77–81. PubMedCrossRefGoogle Scholar
  110. Wang W, Shu D, Chen L et al (2009) Cross-talk between an orphan response regulator and a noncognate histidine kinase in Streptomyces coelicolor. FEMS Microbiol Lett 294:150–156. PubMedCrossRefGoogle Scholar
  111. Wang R, Mast Y, Wang J et al (2013) Identification of two-component system AfsQ1/Q2 regulon and its cross-regulation with GlnR in Streptomyces coelicolor. Mol Microbiol 87:30–48. PubMedCrossRefGoogle Scholar
  112. Wentzel A, Bruheim P, Jakobsen M et al (2012) Optimized submerged batch fermentation strategy for systems scale studies of metabolic switching in Streptomyces coelicolor A3(2). BMC Syst Biol. PubMedPubMedCentralCrossRefGoogle Scholar
  113. Xie Y, Wang B, Liu J et al (2012) Identification of the biosynthetic gene cluster and regulatory cascade for the synergistic antibacterial antibiotics griseoviridin and viridogrisein in Streptomyces griseoviridis. ChemBioChem 13:2745–2757. PubMedCrossRefGoogle Scholar
  114. Xu Y, Liao CH, Yao LL et al (2016) GlnR and PhoP directly regulate the transcription of genes encoding starch-degrading, amylolytic enzymes in Saccharopolyspora erythraea. Appl Environ Microbiol 82:6819–6830. PubMedCentralCrossRefGoogle Scholar
  115. Yang YH, Song E, Kim EJ et al (2009) NdgR, an IclR-like regulator involved in amino-acid-dependent growth, quorum sensing, and antibiotic production in Streptomyces coelicolor. Appl Microbiol Biotechnol 82:501–511. PubMedCrossRefGoogle Scholar
  116. Yang R, Liu X, Wen Y et al (2015) The PhoP transcription factor negatively regulates avermectin biosynthesis in Streptomyces avermitilis. Appl Microbiol Biotechnol 99:10547–10557. PubMedCrossRefGoogle Scholar
  117. Yeo KJ, Kim EH, Hwang E et al (2013) pH-dependent structural change of the extracellular sensor domain of the DraK histidine kinase from Streptomyces coelicolor. Biochem Biophys Res Commun 431:554–559. PubMedCrossRefGoogle Scholar
  118. Yeo KJ, Hong YS, Jee JG et al (2014) Mechanism of the pH-induced conformational change in the sensor domain of the DraK histidine kinase via the E83, E105, and E107 residues. PLoS ONE. CrossRefPubMedPubMedCentralGoogle Scholar
  119. Yim G, Huimi Wang H, Davies FRSJ (2007) Antibiotics as signalling molecules. Philos Trans R Soc B Biol Sci 362:1195–1200. CrossRefGoogle Scholar
  120. Yu H, Yao Y, Liu Y et al (2007) A complex role of Amycolatopsis mediterranei GlnR in nitrogen metabolism and related antibiotics production. Arch Microbiol 188:89–96. PubMedCrossRefGoogle Scholar
  121. Yu Z, Zhu H, Dang F et al (2012) Differential regulation of antibiotic biosynthesis by DraR-K, a novel two-component system in Streptomyces coelicolor. Mol Microbiol 85:535–556. PubMedCrossRefGoogle Scholar
  122. Zothanpuia, Passari AK, Chandra P et al (2017) Production of potent antimicrobial compounds from Streptomyces cyaneofuscatus associated with fresh water sediment. Front Microbiol 8:1–13. CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Alba Romero-Rodríguez
    • 1
  • Nidia Maldonado-Carmona
    • 1
  • Beatriz Ruiz-Villafán
    • 1
  • Niranjan Koirala
    • 1
  • Diana Rocha
    • 1
  • Sergio Sánchez
    • 1
  1. 1.Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoMexico CityMexico

Personalised recommendations