共查询到20条相似文献,搜索用时 93 毫秒
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Combinatorial approaches in metabolic engineering work by generating genetic diversity in a microbial population followed by screening for strains with improved phenotypes. One of the most common goals in this field is the generation of a high rate chemical producing strain. A major hurdle with this approach is that many chemicals do not have easy to recognize attributes, making their screening expensive and time consuming. To address this problem, it was previously suggested to use microbial biosensors to facilitate the detection and quantification of chemicals of interest. Here, we present novel computational methods to: (i) rationally design microbial biosensors for chemicals of interest based on substrate auxotrophy that would enable their high-throughput screening; (ii) predict engineering strategies for coupling the synthesis of a chemical of interest with the production of a proxy metabolite for which high-throughput screening is possible via a designed bio-sensor. The biosensor design method is validated based on known genetic modifications in an array of E. coli strains auxotrophic to various amino-acids. Predicted chemical production rates achievable via the biosensor-based approach are shown to potentially improve upon those predicted by current rational strain design approaches. (A Matlab implementation of the biosensor design method is available via http://www.cs.technion.ac.il/~tomersh/tools). 相似文献
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Metabolic engineering 总被引:2,自引:0,他引:2
Stephanopoulos G 《Biotechnology and bioengineering》1998,58(2-3):119-120
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Metabolic engineering 总被引:9,自引:0,他引:9
Nielsen J 《Applied microbiology and biotechnology》2001,55(3):263-283
Metabolic engineering has developed as a very powerful approach to optimising industrial fermentation processes through the introduction of directed genetic changes using recombinant DNA technology. Successful metabolic engineering starts with a careful analysis of cellular function; based on the results of this analysis, an improved strain is designed and subsequently constructed by genetic engineering. In recent years some very powerful tools have been developed, both for analysing cellular function and for introducing directed genetic changes. In this paper, some of these tools are reviewed and many examples of metabolic engineering are presented to illustrate the power of the technology. The examples are categorised according to the approach taken or the aim: (1) heterologous protein production, (2) extension of substrate range, (3) pathways leading to new products, (4) pathways for degradation of xenobiotics, (5) improvement of overall cellular physiology, (6) elimination or reduction of by-product formation, and (7) improvement of yield or productivity. 相似文献
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V. A. Likhoshvai T. M. Khlebodarova M. T. Ree N. A. Kolchanov 《Applied Biochemistry and Microbiology》2010,46(7):671-687
This review briefs on the main directions in the field of mathematical modeling of metabolic processes aimed at a rational
design of genetically modified organisms. The class of generalized Hill functions is described, and their application to modeling
of nonlinear processes in Escherichia coli metabolic systems is illustrated by several examples. A model for the pyrimidine biosynthesis in E. coli, taking into account the nonlinear effects of a negative allosteric regulation of enzyme activities involved in the control
of the subsequent stages by the end products of synthesis, is considered. It has been shown that the model displays its own
continuous oscillation mode of functioning with a period of approximately 50 min, which is close to the duration of E. coli cell cycle. The need in considering the nonlinear effects in the models as essential elements in the function of metabolic
systems far from equilibrium is discussed. 相似文献
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Metabolic engineering of isoprenoids 总被引:5,自引:0,他引:5
The metabolic engineering of natural products has begun to prosper in the past few years due to genomic research and the discovery of biosynthetic genes. While the biosynthetic pathways and genes for some isoprenoids have been known for many years, new pathways have been found and known pathways have been further investigated. In this article, we review the recent advances in metabolic engineering of isoprenoids, focusing on the molecular genetics that affects pathway engineering the most. Examples in mono- sequi-, and diterpenoid synthesis as well as carotenoid production are discussed. 相似文献
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Yield and productivity are critical for the economics and viability of a bioprocess. In metabolic engineering the main objective
is the increase of a target metabolite production through genetic engineering. Metabolic engineering is the practice of optimizing
genetic and regulatory processes within cells to increase the production of a certain substance. In the last years, the development
of recombinant DNA technology and other related technologies has provided new tools for approaching yields improvement by
means of genetic manipulation of biosynthetic pathway. Industrial microorganisms like Escherichia coli, Actinomycetes, etc. have been developed as biocatalysts to provide new or to optimize existing processes for the biotechnological production
of chemicals from renewable plant biomass. The factors like oxygenation, temperature and pH have been traditionally controlled
and optimized in industrial fermentation in order to enhance metabolite production. Metabolic engineering of bacteria shows
a great scope in industrial application as well as such technique may also have good potential to solve certain metabolic
disease and environmental problems in near future. 相似文献
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Metabolic engineering of gossypol in cotton 总被引:1,自引:0,他引:1
Meiliang Zhou Chengcheng Zhang Yanmin Wu Yixiong Tang 《Applied microbiology and biotechnology》2013,97(14):6159-6165
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Animal cells are widely used in industrial processes as sophisticated cell factories to obtain a high number of complex proteins with correct post-translation modifications and biological activity, with many applications in diagnostic and therapeutic uses. However, from the bioprocess point of view these are still sub-optimal processes, mainly due to the complex requirements for the in vitro growth of the cells, their metabolic and physiological patterns, and the response of mechanisms developed for in vivo growth to the external conditions found in culture in vitro. Metabolic engineering, combined with the corresponding redesign of the process itself, offers the possibility to the enhance the performance of animal cells grown in in vitro systems, targeting how to redesign the cells themselves to make them more robust, efficient, and productive. This paper reviews efforts made in this direction, and how the metabolic engineering of animal cells has been approached to reshape their profiles in various key aspects, namely: central metabolism, protection of apoptosis, regulation of cell cycle, and finally, the combined engineering of different aspects. 相似文献
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Metabolic engineering of the volatile spectrum offers enormous potential for plant improvement because of the great contribution of volatile secondary metabolites to reproduction, defense and food quality. Recent advances in the identification of the genes and enzymes responsible for the biosynthesis of volatile compounds have made this metabolic engineering highly feasible. Notable successes have been reported in enhancing plant defenses and improving scent and aroma quality of flowers and fruits. These studies have also revealed challenges and limitations which will be likely surmounted as our understanding of plant volatile network improves. 相似文献