Universiteit Leiden

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Research project

Streptomyces as cell factories

We aim to engineer streptomycetes to fully exploit their potential for natural product productions, by a rational design and evolution approach.

Gilles van Wezel

As the largest source of antibiotics, the filamentous soil bacteria of the genus Streptomyces are exceptional industrial microorganisms, and a major asset in combating multiple drug-resistant pathogens.

Besides clinical drugs streptomycetes produce a wide variety of industrial enzymes, necessary for the sustainable enzyme-based production of bulk chemicals. Yet streptomycetes are not a preferred industrial host, primarily due to their adverse growth properties resulting from complex mycelial growth and the increasing difficulty to find new lead compounds. To fully exploit streptomycetes as a treasure trove of natural products, major advances are also needed in their engineering, directed at faster growth, lower viscosity of the fermentation broth and efficient product secretion. We replace trial-and-error approaches by a rational design and evolution approach, based on state-of-the-art technologies such as advanced genomics, live imaging-based growth modelling and high resolution imaging.

  • Zacchetti, B., Willemse, J., Recter, B., van Dissel, D., van Wezel, G.P., Wosten, H.A., and Claessen, D. (2016) Aggregation of germlings is a major contributing factor towards mycelial heterogeneity of Streptomyces. Sci Rep 6: 27045.
  • Wu, C., Kim, H.K., van Wezel, G.P., and Choi, Y.H. (2015) Metabolomics in the natural products field - a gateway to novel antibiotics. Drug Discov Today Technol 13: 11-17.
  • van Dissel, D., Claessen, D., and Van Wezel, G.P. (2014) Morphogenesis of Streptomyces in submerged cultures. Adv Appl Microbiol 89: 1-45.
  • van Veluw, G.J., Petrus, M.L., Gubbens, J., de Graaf, R., de Jong, I.P., van Wezel, G.P., Wosten, H.A., and Claessen, D. (2012) Analysis of two distinct mycelial populations in liquid-grown Streptomyces cultures using a flow cytometry-based proteomics approach. Appl Microbiol Biotechnol 96: 1301-1312.
  • Celler, K., Picioreanu, C., van Loosdrecht, M.C., and van Wezel, G.P. (2012) Structured morphological modeling as a framework for rational strain design of Streptomyces species. Antonie Van Leeuwenhoek 102: 409-423.
  • Celler, K., Koning, R.I., Willemse, J., Koster, A.J., and van Wezel, G.P. (2016) Cross-membranes orchestrate compartmentalization and morphogenesis in Streptomyces. Nat Comm 7: 11836.
  • van Wezel, G.P., Krabben, P., Traag, B.A., Keijser, B.J., Kerste, R., Vijgenboom, E., Heijnen, J.J., and Kraal, B. (2006) Unlocking Streptomyces spp. for use as sustainable industrial production platforms by morphological engineering. Appl Environ Microbiol 72: 5283-5288.
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