| 1. |
- Chen, Xiulai, et al.
(författare)
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DCEO Biotechnology: Tools to Design, Construct, Evaluate, and Optimize the Metabolic Pathway for Biosynthesis of Chemicals
- 2018
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Ingår i: Chemical Reviews. - : American Chemical Society (ACS). - 0009-2665 .- 1520-6890. ; 118:1, s. 4-72
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Forskningsöversikt (refereegranskat)abstract
- Chemical synthesis is a well established route for producing many chemicals on a large scale, but some drawbacks still exist in this process, such as unstable intermediates, multistep reactions, complex process control, etc. Biobased production provides an attractive alternative to these challenges, but how to make cells into efficient factories is challenging. As a key enabling technology to develop efficient cell factories, design-construction-evaluation-optimization (DCEO) biotechnology, which incorporates the concepts and techniques of pathway design, pathway construction, pathway evaluation, and pathway optimization at the systems level, offers a conceptual and technological framework to exploit potential pathways, modify existing pathways and create new pathways for the optimal production of desired chemicals. Here, we summarize recent progress of DCEO biotechnology and examples of its application, and provide insights as to when, what and how different strategies should be taken. In addition, we highlight future perspectives of DCEO biotechnology for the successful establishment of biorefineries.
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| 2. |
- Hou, Jianshen, et al.
(författare)
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Rewiring carbon flux in Escherichia coli using a bifunctional molecular switch
- 2020
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Ingår i: Metabolic Engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 61, s. 47-57
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Tidskriftsartikel (refereegranskat)abstract
- The unbalanced distribution of carbon flux in microbial cell factories can lead to inefficient production and poor cell growth. Uncoupling cell growth and chemical synthesis can therefore improve microbial cell factory efficiency. Such uncoupling, which requires precise manipulation of carbon fluxes, can be achieved by up-regulating or down-regulating the expression of enzymes of various pathways. In this study, a dynamic turn-off switch (dTFS) and a dynamic turn-on switch (dTNS) were constructed using growth phase-dependent promoters and degrons. By combining the dTFS and dTNS, a bifunctional molecular switch that could orthogonally regulate two target proteins was introduced. This bifunctional molecular switch was used to uncouple cell growth from shikimic acid and D-glucaric acid synthesis, resulting in the production of 14.33 g/L shikimic acid and the highest reported productivity of D-glucaric acid (0.0325 g/L/h) in Escherichia coli MG1655. This proved that the bifunctional molecular switch could rewire carbon fluxes by controlling target protein abundance.
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| 3. |
- Liu, Liming, 1976, et al.
(författare)
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Use of genome-scale metabolic models for understanding microbial physiology
- 2010
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Ingår i: FEBS Letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 584:12, s. 2556-2564
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Tidskriftsartikel (refereegranskat)abstract
- The exploitation of microorganisms in industrial, medical, food and environmental biotechnology requires a comprehensive understanding of their physiology. The availability of genome sequences and accumulation of high-throughput data allows gaining understanding of microbial physiology at the systems level, and genome-scale metabolic models represent a valuable framework for integrative analysis of metabolism of microorganisms. Genome-scale metabolic models are reconstructed based on a combination of genome sequence information and detailed biochemical information, and these reconstructed models can be used for analyzing and simulating the operation of metabolism in response to different stimuli. Here we discuss the requirement for having detailed physiological insight in order to exploit microorganisms for production of fuels, chemicals and pharmaceuticals. We further describe the reconstruction process of genome-scale metabolic models and different algorithms that can be used to apply these models to gain improved insight into microbial physiology. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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| 4. |
- Ågren, Rasmus, 1982, et al.
(författare)
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The RAVEN Toolbox and Its Use for Generating a Genome-scale Metabolic Model for Penicillium chrysogenum
- 2013
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Ingår i: PLoS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 9:3, s. e1002980-
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Tidskriftsartikel (refereegranskat)abstract
- We present the RAVEN (Reconstruction, Analysis and Visualization of Metabolic Networks) Toolbox: a software suite that allows for semi-automated reconstruction of genome-scale models. It makes use of published models and/or the KEGG database, coupled with extensive gap-filling and quality control features. The software suite also contains methods for visualizing simulation results and omics data, as well as a range of methods for performing simulations and analyzing the results. The software is a useful tool for system-wide data analysis in a metabolic context and for streamlined reconstruction of metabolic networks based on protein homology. The RAVEN Toolbox workflow was applied in order to reconstruct a genome-scale metabolic model for the important microbial cell factory Penicillium chrysogenum Wisconsin54-1255. The model was validated in a bibliomic study of in total 440 references, and it comprises 1471 unique biochemical reactions and 1006 ORFs. It was then used to study the roles of ATP and NADPH in the biosynthesis of penicillin, and to identify potential metabolic engineering targets for maximization of penicillin production.
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