Microbiology

Bacterial gene regulation

The major focus of the research performed in the subgroup headed by Prof. Dr. D. Charlier is on the study of mechanisms of gene expression and gene regulation, and the application of this knowledge in the context of metabolic engineering and synthetic biology. The research group has a long-standing experience and expertise with the unravelling of intricate mechanisms of bacterial gene regulation. Major pathways that are investigated by the team are the biosynthesis of arginine and pyrimidine nucleotides, the uptake and excretion of amino acids, oxidative stress and heavy metal resistance. The research consists of integrated in vivo and in vitro approaches and aims at the characterization of regulatory protein-DNA interactions and the accompanying DNA deformations, protein-protein and protein-effector interactions.

Selected publications

  • Nguyen Le Minh, P., de Cima, S., Bervoets, I., Maes, D. , Rubio, V. & Charlier, D. (2015). Ligand binding specificity of RutR, a member of the TetR family of transcription regulators in Escherichia coli. FEBS Open Bio. 5 (2015) 76-84.
  • Nguyen Le Minh, P., Bervoets, I., Maes, D. & Charlier, D. (2010). The protein-DNA contacts in RutR-carAB operator complexes. Nucleic Acids Research, 38(18): 6286-6300.
  • Nguyen Le Minh, P., Devroede, N., Massant, J., Maes, D. & Charlier, D. (2009). Insights into the architecture and stoichiometry of Escherichia coli PepA-DNA complexes involved in transcriptional control and site-specific DNA recombination by atomic force microscopy. Nucleic Acids Research, 37(5): 1463-1476.
  • Peeters, E., Nguyen Le Minh, P., Foulquié-Moreno, M. & Charlier, D. (2009). Competitive activation of the Escherichia coli argO gene coding for an arginine exporter by the transcriptional regulators Lrp and ArgP. Molecular Microbiology, 74(6): 1513-1526.
  • Caldara, M., Nguyen Le Minh, P., Bostoen, S., Massant, J. & Charlier, D. (2007). ArgR-dependent repression of arginine and histidine transport genes in Escherichia coli K-12. Journal of Molecular Biology, 373(2): 251-267.

Another part of the research aims at the construction of orthogonal regulatory circuits in E. coli for the conditional expression of heterologous genes for the production of complex and high-added value products that are normally not synthesized by this model organism. The generation of such synthetic orthogonal genetic circuits should allow the conditional expression of foreign gene with a minimal interference with the host’s metabolism and should result in optimised gene expression levels and hence more stable production strains and product yields. This work is performed in collaboration with Prof. Dr. ir. Marjan De Mey (UGent).

Selected publications

  • Arense, P., Bernal, V., Charlier, D., Iborra, J., Foulquié-Moreno, M. & Cánovas, M. (2013). Metabolic engineering for high yielding L(-)-carnitine production in Escherichia coli. Microbial Cell Factories, 12(1):56.
  • Waegeman, H., Beauprez, J., Moens, H., Maertens, J., De Mey, M., Foulquié-Moreno, P., Heijnen, J., Charlier, D. & Soetaert, W. (2011). Effect of iclR and arcA knockouts on biomass and metabolic fluxes in Escherichia coli K12 and its implications on understanding the metabolism of Escherichia coli BL21 (DE3). BMC Microbiology, 11:70.
  • Waegeman, H., Beauprez, J., Maertens, J., De Mey, M., Demolder, L., Foulquié-Moreno, P., Boon, N., Charlier, D. & Soetaert, W. (2010). Validation study of 24 deepwell microtiterplates to screen libraries of strains in metabolic engineering. Journal of Bioscience and Bioengineering, 110(6): 646-652.
  • De Mey, M., Lequeux, G., Beauprez, J., Maertens, J., Waegeman, H., Van Bogaert, I., Foulquié-Moreno, P., Charlier, D., Soetaert, W., Vanrolleghem, P. & Vandamme, E. (2010). ∆pppc ppc-p37for recombinant beta-galactosidase production. Journal of Industrial Microbiology and Biotechnology, 37(8): 793-803.