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Old bugs for new tasks; the microbial offer in the proteomics era
Microbial Cell Factories volume 1, Article number: 4 (2002)
Microbial transformations have been unnoticeably exploited by mankind for centuries especially in the context of early food industries. The modern biotechnology uses microbial cells in a more directed approach to produce enzymes, antibiotics, amino acids and other metabolites of economical interest. Food and mining industries are also sustained by natural microbial activities tailored in a way that favours the desired transformations. The birth of genetic engineering in the late 70's and its further technical expansion have provided molecular tools to engineer and produce hetereologous proteins in a diversity of microorganisms including bacteria, yeast and filamentous fungi, thus largely extending their manufacturing capabilities.
Nowadays, the main sources of proteins for research are genetically modified microorganisms. However, industrial production of such proteins has not been as successful as initially expected and in many cases, the yield of the processes is low and hard to justify, from an economical point of view, a large-scale recombinant production. Producer cells commonly suffer from protein-promoted toxicity, often resulting in slow growth, cell death and plasmid instability. On the other side, recombinant proteins, apart from overloading the cells with extra metabolic demands, often undergo proteolysis and/or aggregate as inactive polypeptides into inclusion bodies. These events derive from the incapability of foreign proteins, as produced at high non-physiological rates, to fold into their native conformation. Although the exploration of different cell systems can permit to escape from the above listed obstacles (that on the other hand, are rather unpredictable for a given protein), some of them can be surmounted by genetic, protein and metabolic engineering approaches and/or by process and downstream optimisation. Intriguingly, the emerging need for a wide-spectrum, efficient protein production in the proteomics era has favoured a deeper analysis of the recombinant cell physiology. In this regard, scientists have turned their attention to the cells rather than merely observing the products. The Cell Factory concept is then completely structured through the examination of the metabolic capabilities of the producer cells in close relationship with the nature and features of the product (recombinant or not) and the production process itself. The consequent identification of main bottlenecks encountered during production, as well as the cell responses triggered under this situation reveals the integrated nature and complexity of the machinery involved in biosynthesis and quality control and also its connexions with the mechanisms coping with stress at both cellular and populational levels. Based on these findings, we can now better approach improved strategies to adapt old microbes to new production requirements for both natural and engineered products.
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Villaverde, A. Old bugs for new tasks; the microbial offer in the proteomics era. Microb Cell Fact 1, 4 (2002). https://doi.org/10.1186/1475-2859-1-4