| 1. |
- Campbell, Kate, 1987, et al.
(författare)
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The Impact of Systems Biology on Bioprocessing
- 2017
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Ingår i: Trends in Biotechnology. - : Elsevier BV. - 0167-7799 .- 1879-3096. ; 35:12, s. 1156-1168
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Forskningsöversikt (refereegranskat)abstract
- Bioprocessing offers a sustainable and green approach to the production of chemicals. However, a bottleneck in introducing bioprocesses is cell factory development, which is costly and time-consuming. A systems biology approach can expedite cell factory design by using genome-wide analyses alongside mathematical modeling to characterize and predict cellular physiology. This approach can drive cycles of design, build, test, and learn implemented by metabolic engineers to optimize the cell factory performance. Streamlining of the design phase requires a clearer understanding of metabolism and its regulation, which can be achieved using quantitative and integrated omic characterization, alongside more advanced analytical methods. We discuss here the current impact of systems biology and challenges of closing the gap between bioprocessing and more traditional methods of chemical production.
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| 2. |
- Chen, Min, et al.
(författare)
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Yeast increases glycolytic flux to support higher growth rates accompanied by decreased metabolite regulation and lower protein phosphorylation
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 120:25
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Tidskriftsartikel (refereegranskat)abstract
- Supply of Gibbs free energy and precursors are vital for cellular function and cell metabolism have evolved to be tightly regulated to balance their supply and consumption. Precursors and Gibbs free energy are generated in the central carbon metabolism (CCM), and fluxes through these pathways are precisely regulated. However, how fluxes through CCM pathways are affected by posttranslational modification and allosteric regulation remains poorly understood. Here, we integrated multi-omics data collected under nine different chemostat conditions to explore how fluxes in the CCM are regulated in the yeast Saccharomyces cerevisiae. We deduced a pathway- and metabolism-specific CCM flux regulation mechanism using hierarchical analysis combined with mathematical modeling. We found that increased glycolytic flux associated with an increased specific growth rate was accompanied by a decrease in flux regulation by metabolite concentrations, including the concentration of allosteric effectors, and a decrease in the phosphorylation level of glycolytic enzymes.
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| 3. |
- Qin, Ning, 1990, et al.
(författare)
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Flux regulation through glycolysis and respiration is balanced by inositol pyrophosphates in yeast
- 2023
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 186:4, s. 748-763.e15
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Tidskriftsartikel (refereegranskat)abstract
- Although many prokaryotes have glycolysis alternatives, it's considered as the only energy-generating glucose catabolic pathway in eukaryotes. Here, we managed to create a hybrid-glycolysis yeast. Subsequently, we identified an inositol pyrophosphatase encoded by OCA5 that could regulate glycolysis and respiration by adjusting 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-InsP7) levels. 5-InsP7 levels could regulate the expression of genes involved in glycolysis and respiration, representing a global mechanism that could sense ATP levels and regulate central carbon metabolism. The hybrid-glycolysis yeast did not produce ethanol during growth under excess glucose and could produce 2.68 g/L free fatty acids, which is the highest reported production in shake flask of Saccharomyces cerevisiae. This study demonstrated the significance of hybrid-glycolysis yeast and determined Oca5 as an inositol pyrophosphatase controlling the balance between glycolysis and respiration, which may shed light on the role of inositol pyrophosphates in regulating eukaryotic metabolism.
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| 4. |
- Qin, Ning, et al.
(författare)
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Increased CO 2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeast
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- CO2 fixation plays a key role to make biobased production cost competitive. Here, we use 3-hydroxypropionic acid (3-HP) to showcase how CO2 fixation enables approaching theoretical-yield production. Using genome-scale metabolic models to calculate the production envelope, we demonstrate that the provision of bicarbonate, formed from CO2, restricts previous attempts for high yield production of 3-HP. We thus develop multiple strategies for bicarbonate uptake, including the identification of Sul1 as a potential bicarbonate transporter, domain swapping of malonyl-CoA reductase, identification of Esbp6 as a potential 3-HP exporter, and deletion of Uga1 to prevent 3-HP degradation. The combined rational engineering increases 3-HP production from 0.14 g/L to 11.25 g/L in shake flask using 20 g/L glucose, approaching the maximum theoretical yield with concurrent biomass formation. The engineered yeast forms the basis for commercialization of bio-acrylic acid, while our CO2 fixation strategies pave the way for CO2 being used as the sole carbon source.
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| 5. |
- Xia, Jianye, 1980, et al.
(författare)
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Proteome allocations change linearly with the specific growth rate of Saccharomyces cerevisiae under glucose limitation
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Saccharomyces cerevisiae is a widely used cell factory; therefore, it is important to understand how it organizes key functional parts when cultured under different conditions. Here, we perform a multiomics analysis of S. cerevisiae by culturing the strain with a wide range of specific growth rates using glucose as the sole limiting nutrient. Under these different conditions, we measure the absolute transcriptome, the absolute proteome, the phosphoproteome, and the metabolome. Most functional protein groups show a linear dependence on the specific growth rate. Proteins engaged in translation show a perfect linear increase with the specific growth rate, while glycolysis and chaperone proteins show a linear decrease under respiratory conditions. Glycolytic enzymes and chaperones, however, show decreased phosphorylation with increasing specific growth rates; at the same time, an overall increased flux through these pathways is observed. Further analysis show that even though mRNA levels do not correlate with protein levels for all individual genes, the transcriptome level of functional groups correlates very well with its corresponding proteome. Finally, using enzyme-constrained genome-scale modeling, we find that enzyme usage plays an important role in controlling flux in amino acid biosynthesis. Understanding how yeast organizes its functional proteome is a fundamental task in systems biology. Here, the authors conduct a multiomics analysis on yeast cells cultured with different growth rates, identifying a linear dependence of the functional proteome on the growth rate.
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| 6. |
- Xie, Tingting, et al.
(författare)
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Multi-omics analyses of the transition to the Crabtree effect in S. cerevisiae reveals a key role for the citric acid shuttle
- 2022
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Ingår i: FEMS Yeast Research. - : Oxford University Press (OUP). - 1567-1356 .- 1567-1364. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- The article investigates the Crabtree effect under dynamic process which have never been reported, and find the citric acid shuttles to support higher demand of alpha-ketoglutarate under Crabtree effect. The Crabtree effect in the yeast, Saccharomyces cerevisiae, has been extensively studied, but only few studies have analyzed the dynamic conditions across the critical specific growth rate where the Crabtree effect sets in. Here, we carried out a multi-omics analysis of S. cerevisiae undergoing a specific growth rate transition from 0.2 h(-1) to 0.35 h(-1). The extracellular metabolome, the transcriptome and the proteome were analyzed in an 8-h transition period after the specific growth rate shifted from 0.2 h(-1) to 0.35 h(-1). The changing trends of both the transcriptome and proteome were analyzed using principal component analysis, which showed that the transcriptome clustered together after 60 min, while the proteome reached steady-state much later. Focusing on central carbon metabolism, we analyzed both the changes in the transcriptome and proteome, and observed an interesting changing pattern in the tricarboxylic acid (TCA) pathway, which indicates an important role for citric acid shuttling across the mitochondrial membrane for alpha-ketoglutarate accumulation during the transition from respiratory to respiro-fermentative metabolism. This was supported by a change in the oxaloacetate and malate shuttle. Together, our findings shed new light into the onset of the Crabtree effect in S. cerevisiae.
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| 7. |
- Yang, Junhuai, et al.
(författare)
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Holocene forcing of aeolian dust activity over the Tibetan Plateau and its surroundings
- 2024
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Ingår i: Global and Planetary Change. - 0921-8181 .- 1872-6364. ; 235
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Tidskriftsartikel (refereegranskat)abstract
- Aeolian deposits on the Tibetan Plateau (TP) and its surroundings provide crucial source materials for the Asian dust cycle, which significantly affects Asian and global ecosystems and climate. However, it is unclear how the dust dynamics of the TP and its surroundings are linked to Earth's climate system. To address this issue, we examined the grain size and accumulation rate of six Holocene aeolian sections on the southern TP (a new, well-dated high-resolution section, two relatively low-resolution sections, and three published sections) and combined them with equivalent aeolian sedimentary records from eastern arid central Asia. The results suggest that dust activity in both regions decreased during the early to middle Holocene and then increased in the late Holocene. We hypothesize that the primary drivers of Holocene dust activity in both regions are similar. Cold-season insolation, as the primary driving factor, combined with ice volume and atmospheric CO2 concentration, collectively controlled the regional temperature, which determined the near-surface wind intensity via its influence on the TP High and Siberian High, respectively, thus ultimately controlling the regional dust activity. In this context, we project that dust activity on the TP and its neighboring areas will decrease under warm scenarios in the 21st century. Overall, our findings provide an extensive overview of the past, present, and future scenarios of Asian dust activity, especially of the TP dust.
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