Skip to main content

Systems biology and biological systems diversity for the engineering of microbial cell factories

Metabolic engineering was originally conceived as a systems approach to optimise biotechnologically desired traits of microbes and higher cells [1]. Microbial Cell Factories has published several review and research articles on this field over the past recent years [28]. Although clear breakthroughs have been achieved in the past, progress in metabolic engineering has been largely limited to individual pathways or relatively simple networks. Engineering of complex metabolic networks has been hampered by the insufficient biological information and global analytical tools.

Systems biology is increasingly generating a quantitative knowledge base of cell physiology, offering, for the first time, insights into molecular/cellular processes and function at a cell-wide scale. In order for metabolic/cellular engineers to embrace the potential that systems biology offers, an understanding of a variety of analytical and mathematical/computational tools is required [912]. However, whilst our knowledge on the systems components (genes, proteins, metabolites) has increased significantly, data integration in computer models with appropriate mechanistic and molecular detail to enable in silico experiments of sufficient predictive capability is still limiting the increase in the success rate of microbial cell factories engineering strategies.

Microbial Cell Factories is already contributing to individual systems biology-driven technological and methodological advances, experimental (at the transcriptomic [1315], proteomic [16] and metabolomic/fluoxomic levels [1720]) or computational [21, 22]. Whilst strengthening this trend, we would also like to expand our field of interest to the integration of experimental data with computational and theoretical methods by encouraging the publication of research and review articles covering core aspects of the application of systems biology to the engineering of microbial cell factories (i.e. metabolic or cellular engineering). Moreover, the growing number of host cell systems being explored as factories, the continuous improvement of genetic tools, progress in de novo synthesis of increasingly complex biological entities (synthetic biology [23]) and, the growing diversity of bioproducts, is creating an emerging interest to extend our knowledge base to cell factories other than the classic model organisms. Also, a comparative analysis amongst different organisms is expected to yield new insights in cellular processes and function.

While of general interest in the green and white biotechnology, we believe our initiative will also contribute to fulfil the changing needs within highly specialized technical and scientific areas in biomedicine and biotechnology.

References

  1. Bailey JE: Toward a science of metabolic engineering. Science. 1991, 252: 1668-1675. 10.1126/science.2047876.

    Article  CAS  Google Scholar 

  2. Gosset G: Improvement of Escherichia coli production strains by modification of the phosphoenolpyruvate:sugar phosphotransferase system. Microb Cell Fact. 2005, 4: 14-10.1186/1475-2859-4-14.

    Article  Google Scholar 

  3. Sørensen HP, Mortensen KK: Soluble expression of recombinant proteins in the cytoplasm of Escherichia coli. Microb Cell Fact. 2005, 4: 1-10.1186/1475-2859-4-1.

    Article  Google Scholar 

  4. Ruffing A, Chen RR: Metabolic engineering of microbes for oligosaccharide and polysaccharide synthesis. Microb Cell Fact. 2006, 5: 25-10.1186/1475-2859-5-25.

    Article  Google Scholar 

  5. Chemler JA, Yan Y, Koffas MAG: Biosynthesis of isoprenoids, polyunsaturated fatty acids and flavonoids in Saccharomyces cerevisiae. Microb Cell Fact. 2006, 5: 20-10.1186/1475-2859-5-20.

    Article  Google Scholar 

  6. Karhumaa K, Wiedemann B, Hahn-Hägerdal B, Boles E, Gorwa-Grauslund M-F: Co-utilization of L-arabinose and D-xylose by laboratory and industrial Saccharomyces cerevisiae strains. Microb Cell Fact. 2006, 5: 18-10.1186/1475-2859-5-18.

    Article  Google Scholar 

  7. Branduardi P, Sauer M, de Gioia L, Zampella G, Valli M, Mattanovich D, Porro D: Lactate production yield from engineered yeasts is dependent from the host background, the lactate dehydrogenase source and the lactate export. Microb Cell Fact. 2006, 5: 4-10.1186/1475-2859-5-4.

    Article  Google Scholar 

  8. Bernal V, Sevilla A, Canovas M, Iborra JL: Production of L-carnitine by secondary metabolism of bacteria. Microb Cell Fact. 2007, 6: 31-10.1186/1475-2859-6-31.

    Article  Google Scholar 

  9. Stephanopoulos G, Alper H, Moxley J: Exploiting biological complexity for strain improvement through systems biology. Nat Biotechnol. 2004, 22: 1261-1267. 10.1038/nbt1016.

    Article  CAS  Google Scholar 

  10. Lee SY, Lee DY, Kim TY: Systems biotechnology for strain improvement. Trends Biotechnol. 2005, 23: 349-358. 10.1016/j.tibtech.2005.05.003.

    Article  CAS  Google Scholar 

  11. Stelling J: Mathematical models in microbial systems biology. Curr Opin Microbiol. 2004, 7: 513-518. 10.1016/j.mib.2004.08.004.

    Article  Google Scholar 

  12. Alves R, Antunes F, Salvador A: Tools for kinetic modelling of biochemical networks. Nat Biotechnol. 2006, 24: 667-672. 10.1038/nbt0606-667.

    Article  CAS  Google Scholar 

  13. Jaluria P, Konstantopoulos K, Betenbaugh M, Shiloach J: A perspective on microarrays: current applications, pitfalls, and potential uses. Microb Cell Fact. 2007, 6: 4-10.1186/1475-2859-6-4.

    Article  Google Scholar 

  14. Baez-Viveros JL, Flores N, Suarez K, Castillo-Espana P, Bolivar F, Gosset G: Metabolic transcription analysis of engineered Escherichia coli strains that overproduce L-phenylalanine. Microb Cell Fact. 2007, 6: 30-10.1186/1475-2859-6-30.

    Article  Google Scholar 

  15. Sauer M, Branduardi P, Gasser B, Valli M, Maurer M, Porro D, Mattanovich D: Differential gene expression in recombinant Pichia pastoris analysed by heterologous DNA microarray hybridisation. Microb Cell Fact. 2004, 3: 17-10.1186/1475-2859-3-17.

    Article  Google Scholar 

  16. Graham RLJ, Graham C, McMullan G: Microbial proteomics: a mass spectrometry primer for biologists. Microb Cell Fact. 2007, 6: 26-10.1186/1475-2859-6-26.

    Article  Google Scholar 

  17. Frick O, Wittmann C: Characterization of the metabolic shift between oxidative and fermentative growth in Saccharomyces cerevisiae by comparative 13C flux analysis. Microb Cell Fact. 2005, 4: 30-10.1186/1475-2859-4-30.

    Article  Google Scholar 

  18. Wittmann C: Fluxome analysis using GC-MS. Microb Cell Fact. 2007, 6: 6-10.1186/1475-2859-6-6.

    Article  Google Scholar 

  19. Faijes M, Mars AE, Smid EJ: Comparison of quenching and extraction methodologies for metabolome analysis of Lactobacillus plantarum. Microb Cell Fact. 2007, 6: 27-10.1186/1475-2859-6-27.

    Article  Google Scholar 

  20. Shirai T, Fujimura K, Furusawa C, Nagahisa K, Shioya S, Shimizu H: Study on roles of anaplerotic pathways in glutamate overproduction of Corynebacterium glutamicum by metabolic flux analysis. Microb Cell Fact. 2007, 6: 19-10.1186/1475-2859-6-19.

    Article  Google Scholar 

  21. Bansal AK: Bioinformatics in microbial biotechnology – a mini review. Microb Cell Fact. 2005, 4: 19-10.1186/1475-2859-4-19.

    Article  Google Scholar 

  22. Tsantili IC, Karim MN, Klapa MI: Quantifying the metabolic capabilities of engineered Zymomonas mobilis using linear programming analysis. Microb Cell Fact. 2007, 6: 8-10.1186/1475-2859-6-8.

    Article  Google Scholar 

  23. Heinemann M, Panke S: Synthetic biology – putting engineering into biology. Bioinformatics. 2006, 22: 2790-2799. 10.1093/bioinformatics/btl469.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pau Ferrer.

Rights and permissions

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Cite this article

Ferrer, P. Systems biology and biological systems diversity for the engineering of microbial cell factories. Microb Cell Fact 6, 35 (2007). https://doi.org/10.1186/1475-2859-6-35

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/1475-2859-6-35