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Metabolic engineering is the practice of optimizing genetic and regulatory processes within cells to increase the cells' production of a certain substance. These processes are chemical networks that use a series of biochemical reactions and enzymes that allow cells to convert raw materials into molecules necessary for the cell’s survival. Metabolic engineering specifically seeks to mathematically model these networks, calculate a yield of useful products, and pin point parts of the network that constrain the production of these products.〔Yang, Y.T., Bennet, G. N., San, K.Y., (1998) ''Genetic and Metabolic Engineering'', Electronic Journal of Biotechnology, ISSN 07117-3458〕 Genetic engineering techniques can then be used to modify the network in order to relieve these constraints. Once again this modified network can be modeled to calculate the new product yield. The ultimate goal of metabolic engineering is to be able to use these organisms to produce valuable substances on an industrial scale in a cost effective manner. Current examples include producing beer, wine, cheese, pharmaceuticals, and other biotechnology products. Since cells use these metabolic networks for their survival, changes can have drastic effects on the cells' viability. Therefore, trade-offs in metabolic engineering arise between the cells ability to produce the desired substance and its natural survival needs. Therefore, instead of directly deleting and/or overexpressing the genes that encode for metabolic enzymes, the current focus is to target the regulatory networks in a cell to efficiently engineer the metabolism.〔Vemuri, G.M, Aristidou, A.A, (2005) ''Metabolic Engineering in the -omics Era: Elucidating and Modulating Regulatory Networks'', Microbial Mol Biology Review vol. 69: 197-216〕 == History and applications of metabolic engineering == In the past, to increase the productivity of a desired metabolite, a microorganism was genetically modified by chemically induced mutation, and the mutant strain that overexpressed the desired metabolite was then chosen.〔Voit,Eberhard.,Torres,Nestor V.(2002)." Pathways Analysis and Optimization in Metabolic Engineering." Cambridge:University Press,p.ix-x〕 However, one of the main problems with this technique was that the metabolic pathway for the production of that metabolite was not analyzed, and as a result, the constraints to production and relevant pathway enzymes to be modified were unknown.〔 In 1990s, a new technique called metabolic engineering emerged. This technique analyzes the metabolic pathway of a microorganism, and determines the constraints and their effects on the production of desired compounds. It then uses genetic engineering to relieve these constraints. Some examples of successful metabolic engineering are the following: (i) Identification of constraints to lysine production in corynebacterium ''glutamicum'' and insertion of new genes to relieve these constraints to improve production〔Stephanopoulos, G. N., Aristidou, A. A., Nielsen, J. (1998). " Metabolic Engineering: Principles and Methodologies ". San Diego: Academic Press〕 (ii) Engineering of a new fatty acid biosynthesis pathway, called reversed beta oxidation pathway, that is more efficient than the native pathway in producing fatty acids and alcohols which can potentially be catalytically converted to chemicals and fuels〔Dellomonaco, Clementina.(2011). '' Engineered Reversal of the beta oxidation cycle for the Synthesis of Fuels and Chemicals.'' Nature 476,355-359〕 (iii) Improved production of DAHP an aromatic metabolite produced by ''E.coli'' that is an intermediate in the production of aromatic amino acids.〔Patnaik, R. and Liao, J. (1994). "Engineering of Escherichia coli central metabolism for aromatic metabolite production with near theoretical yield". ''Appl. Environ. Microbiol.'' 60(11):3903-3908〕 It was determined through metabolic flux analysis that the theoretical maximal yield of DAHP per glucose molecule utilized, was 3/7. This is because some of the carbon from glucose is lost as carbon dioxide, instead of being utilized to produce DAHP. Also, one of the metabolites (PEP, or phosphoenolpyruvate) that are used to produce DAHP, was being converted to pyruvate (PYR) to transport glucose into the cell, and therefore, was no longer available to produce DAHP. In order to relieve the shortage of PEP and increase yield, Patnaik et al. used genetic engineering on ''E.coli'' to introduce a reaction that converts PYR back to PEP. Thus, the PEP used to transport glucose into the cell is regenerated, and can be used to make DAHP. This resulted in a new theoretical maximal yield of 6/7 - double that of the native ''E.coli'' system. At the industrial scale, metabolic engineering is becoming more convenient and cost effective. According to the Biotechnology Industry Organization, " more than 50 biorefinery facilities are being built across North America to apply metabolic engineering to produce biofuels and chemicals from renewable biomass which can help reduce greenhouse gas emissions ". Potential biofuels include short-chain alcohols and alkanes (to replace gasoline), fatty acid methyl esters and fatty alcohols (to replace diesel), and fatty acid-and isoprenoid-based biofuels (to replace diesel).〔Keasling D.,Jay(2010).'' Advanced Biofuel production in microbes.'' Biotechnol.J.,5,147-162〕 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Metabolic engineering」の詳細全文を読む スポンサード リンク
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