Molecular Systems Microbiology: exploring omics approaches focusing Food and Bioethanol Industries
Team : Isabel Sá-Correia, Miguel C Teixeira, Nuno P Mira, Margarida Palma and the PhD students: Joana Guerreiro, Filipa Roque, Sílvia Henriques.
Systems Biology is an emerging field that aims at the understanding of biological problems at a system's level, focusing on interactions between a multitude of components. Systems biology relies on the ability to obtain a 'global' view of the physiology of a cell by the simultaneous identification and quantification of thousands of different molecules (such as proteins, nucleic acids, metabolites….) and by studying the relationships and complex interactions between these key elements and various parts of a biological system. The techniques used to acquire data are based in the various 'omics' approaches (transcriptomics, proteomics, metabolomics, glycomics, lipidomics, interactomics…), as well as in high-throughput genetics.Complex molecular biological systems can be described accordingly, based on the integration of genome-wide data and using appropriate computational tools.
1. Food production and preservation
The success of food and beverage production processes carried out by the yeast Saccharomyces cerevisiae of Biotechnological relevance and the thriving of food spoilage fungi are dependent on the ability of the cell to cope with the many environmental insults imposed during food production and preservation processes. The use of yeast as a cell factory or as a model food spoilage yeast and the exploitation of post-genomics approaches are providing clues, at a systems level, for the identification of: 1) candidate target genes for genetic engineering of stress tolerant industrial yeast strains; 2) molecular targets for new food preservation strategies; 3) biomarker molecules for the early prediction of food production process outcome. T he mechanisms behind resistance to weak acids used as food preservatives, in particular acetic and propionic acids in S. cerevisiae and in the highly acetic acid resistant spoilage yeast Zygosaccharomyces bailii, are being examined, using transcriptomics, proteomics, metabolomics and chemogenomics approaches.
2. Bioethanol production
Chemogenomics, expression proteomics, transcriptomics, and NMR-based metabolomics are being explored to reveal the mechanisms of toxicity, the environmental responses and the signaling pathways underlying the adaptive response of S. cerevisiae to stresses occurring during industrial bioethanol production processes.
Specifically, the mechanisms of toxicity of, and yeast tolerance to, high concentrations of ethanol, glucose and acetic acid, the stresses that limit alcoholic fermentation performance in bioethanol or wine production processes, are being analysed. In an effort to design yeast strains, fermentation media and conditions that can be used in second generation bioethanol production processes, the mechanisms of tolerance to stress imposed by side-products of the hydrolysis of lignocellulosic raw materials are also being evaluated. Gene and genomic expression changes occurring under stresses relevant to industrial alcoholic fermentation are being studied, focusing on signalling pathways, transcription factors (Haa1 and Rim101) and target genes. The INTACT Project in the frame of the ERA-NET Industrial Biotechnology will further focus on the integral engineering of acetic acid tolerance in yeast.
- dos Santos, S.C., Sá-Correia, I., "Yeast toxicogenomics: lessons from a eukaryotic cell model and cell factory", Current Opinion in Biotechnology 33:183–191, 2015.
- Mira, N.P., Münsterkötter, M., Dias-Valada, F., Santos, J., Palma, M., Roque, F., Guerreiro, J., Rodrigues, F., Sousa, M.J., Leão, C., Guldener, U., Sá-Correia, I., "The genome sequence of the highly acetic acid-tolerant Zygosaccharomyces bailii derived interspecies hybrid strain ISA1307, isolated from a sparkling wine plant", DNA Research, 21(3):299-313, 2014.
- Lourenço, A.B., Roque, F.C., Teixeira, M.C., Ascenso, J.R., Sá-Correia, I., "Quantitative 1H-NMR-metabolomics reveals extensive metabolic reprogramming and the effect of the aquaglyceroporin FPS1 in ethanol stressed yeast cells", PLoS One, 8 (2): e55439, 2013.
- Guerreiro, J., Mira, N.P., Sá-Correia, I., "Adaptive response to acetic acid in the highly resistant species Zygosaccharomyces bailii revealed by quantitative proteomics", PROTEOMICS, 12: 2303-18, 2012.
- Madeira, A., da Silva, C.L, dos Santos, F., Camafeita, E., Cabral, J.M.S., Sá-Correia, I., "Human Mesenchymal Stem Cell Expression program upon extended ex-vivo cultivation as revealed by 2-DE-Based quantitative proteomics", PLOS One, 7(8), 2012.
- Mira, N.P., Henriques, S., Keller, G., Teixeira, M.C., Matos, R., Arraiano, C., Winge, D.R., Sá-Correia, I., Identification of a DNA binding site for the transcription factor Haa1p, required for Saccharomyces cerevisiae response to acetic acid stress. Nucleic Acids Research , 16, 6896-6907, 2011.
- Teixeira, M.C., Mira, N.P., Sá-Correia, I., "A genome-wide perspective on the response and tolerance to food-relavant stresses in Saccharomyces cerevisiae",Current Opinion in Biotechnology , 22: 150-156, 2011.
- Mira, N.P., Becker, J.D., Sá-Correia, I. , "Genomic expression program involving the Haa1p-regulon in Saccharomyces cerevisiae response to acetic acid", OMICS: a Journal of Integrative Biology , 14(5), 587-601, 2010.
- dos Santos, S.C., Mira, N.P., Moreira, A.S., Sá-Correia, I., "Quantitative- and phospho-proteomic analysis of the yeast response to the tyrosine kinase inhibitor imatinib", OMICS: A Journal of Integrative Biology, 16(10), 537-551, 2012.
- Teixeira, M.C., Raposo, L.R., Mira, N.P., Lourenço, A.B., Sá-Correia, I., "Genome-wide identification of genes required for maximal tolerance to ethanol in yeast: important role of FPS1" Applied Environmental Microbiology, 75: 5761-5772, 2009.