| 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. |
- Ye, Chao, et al.
(författare)
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Comprehensive understanding of Saccharomyces cerevisiae phenotypes with whole-cell model WM_S288C
- 2020
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Ingår i: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 117:5, s. 1562-1574
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Tidskriftsartikel (refereegranskat)abstract
- Biological network construction for Saccharomyces cerevisiae is a widely used approach for simulating phenotypes and designing cell factories. However, due to a complicated regulatory mechanism governing the translation of genotype to phenotype, precise prediction of phenotypes remains challenging. Here, we present WM_S288C, a computational whole-cell model that includes 15 cellular states and 26 cellular processes and which enables integrated analyses of physiological functions of Saccharomyces cerevisiae. Using WM_S288C to predict phenotypes of S. cerevisiae, the functions of 1140 essential genes were characterized and linked to phenotypes at five levels. During the cell cycle, the dynamic allocation of intracellular molecules could be tracked in real-time to simulate cell activities. Additionally, one-third of non-essential genes were identified to affect cell growth via regulating nucleotide concentrations. These results demonstrated the value of WM_S288C as a tool for understanding and investigating the phenotypes of S. cerevisiae.
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