Universiteit Leiden

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Research project

Regulatory networks in Streptomyces

We aim to unravel the complex and intertwining regulatory systems that control development and antibiotic production in streptomycetes.

Gilles van Wezel

Streptomycetes require a large number of regulatory proteins to control metabolism and growth, as well as morphological, physiological and chemical differentiation. Complex and intertwining regulatory networks, consisting of pathway-specific and global transcriptional regulators, are in place to translate environmental signals into appropriate cellular responses. We aim to unravel the systems that control development and antibiotic production, two closely linked processes, for strain improvement purposes.

One of the most extensively studied regulators in streptomycetes is the pleiotropic global regulator DasR, which represses antibiotic production and development. DasR directly controls these processes, including all antibiotic biosynthetic gene clusters in S. coelicolor, and recent evidence suggests similar control is widespread among actinomycetes. In our lab, we extensively study the regulatory role of DasR and its link to N-acetylglucosamine metabolism, which modulates the activity of this global repressor, as well as other important regulators of development and antibiotic production.

  • Urem, M., Swiatek-Polatynska, M.A., Rigali, S., and van Wezel, G.P. (2016) Intertwining nutrient-sensory networks and the control of antibiotic production in Streptomyces. Mol Microbiol. 102 (2), 183-195.
  • Urem, M., van Rossum, T., Bucca, G., Moolenaar, G.F., Laing, E., Swiatek-Polatynska, M.A., Willemse, J., Tenconi, E., Rigali, S., Goosen, N., Smith, C.P., and van Wezel, G.P. (2016b) OsdR of Streptomyces coelicolor and the Dormancy Regulator DevR of Mycobacterium tuberculosis Control Overlapping Regulons. mSystems 1.
  • Świątek-Połatyńska, M.A., Bucca, G., Laing, E., Gubbens, J., Titgemeyer, F., Smith, C.P., Rigali, S., and van Wezel, G.P. (2015) Genome-wide analysis of in vivo binding of the master regulator DasR in Streptomyces coelicolor identifies novel non-anonical targets. PLoS ONE 10: e0122479.
  • Swiatek, M.A., Gubbens, J., Bucca, G., Song, E., Yang, Y.H., Laing, E., Kim, B.G., Smith, C.P., and van Wezel, G.P. (2013) The ROK family regulator Rok7B7 pleiotropically affects xylose utilization, carbon catabolite repression, and antibiotic production in Streptomyces coelicolor. J Bacteriol 195: 1236-1248.
  • Rigali, S., Titgemeyer, F., Barends, S., Mulder, S., Thomae, A.W., Hopwood, D.A., and van Wezel, G.P. (2008) Feast or famine: the global regulator DasR links nutrient stress to antibiotic production by Streptomyces. EMBO Rep 9: 670-675.
  • van Wezel, G.P., and McDowall, K.J. (2011) The regulation of the secondary metabolism of Streptomyces: new links and experimental advances. Nat Prod Rep 28: 1311-1333.
  • Rigali, S., Nothaft, H., Noens, E.E., Schlicht, M., Colson, S., Muller, M., Joris, B., Koerten, H.K., Hopwood, D.A., Titgemeyer, F., and van Wezel, G.P. (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.
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