| 1. |
- 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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| 2. |
- 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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| 3. |
- Qin, Ning, et al.
(författare)
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Rewiring Central Carbon Metabolism Ensures Increased Provision of Acetyl-CoA and NADPH Required for 3-OH-Propionic Acid Production
- 2020
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Ingår i: ACS Synthetic Biology. - : American Chemical Society (ACS). - 2161-5063. ; 9:12, s. 3236-3244
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Tidskriftsartikel (refereegranskat)abstract
- The central carbon metabolite acetyl-CoA and the cofactor NADPH are important for the synthesis of a wide array of biobased products. Here, we constructed a platform yeast strain for improved provision of acetyl-CoA and NADPH, and used the production of 3-hydroxypropionic acid (3-HP) as a case study. We first demonstrated that the integration of phosphoketolase and phosphotransacetylase improved 3-HP production by 41.9% and decreased glycerol production by 48.1% compared with that of the control strain. Then, to direct more carbon flux toward the pentose phosphate pathway, we reduced the expression of phosphoglucose isomerase by replacing its native promoter with a weaker promoter, and increased the expression of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by replacing their native promoters with stronger promoters. This further improved 3-HP production by 26.4%. Furthermore, to increase the NADPH supply we overexpressed cytosolic aldehyde dehydrogenase, and improved 3-HP production by another 10.5%. Together with optimizing enzyme expression of acetyl-CoA carboxylase and malonyl-CoA reductase, the final strain is able to produce 3-HP with a final titer of 864.5 mg/L, which is a more than 24-fold improvement compared with that of the starting strain. Our strategy combines the PK pathway with the oxidative pentose phosphate pathway for the efficient provision of acetyl-CoA and NADPH, which provides both a higher theoretical yield and overall yield than the reported yeast-based 3-HP production strategies via the malonyl-CoA reductase-dependent pathway and sheds light on the construction of efficient platform cell factories for other products.
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| 4. |
- Zhang, Shuangshuang, et al.
(författare)
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Narrow-gap, semiconducting, superhard amorphous carbon with high toughness, derived from C60 fullerene
- 2021
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Ingår i: Cell Reports Physical Science. - : Elsevier. - 2666-3864. ; 2:9
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Tidskriftsartikel (refereegranskat)abstract
- New carbon forms that exhibit extraordinary physicochemical properties can be generated from nanostructured precursors under extreme pressure. Nevertheless, synthesis of such fascinating materials is often not well understood. That is the case of the C60 precursor, with irreproducible results that impede further progress in the materials design. Here, the semiconducting amorphous carbon, having band gaps of 0.1–0.3 eV and the advantages of isotropic superhardness and superior toughness over single-crystal diamond and inorganic glasses, is produced from fullerene at high pressure and moderate temperatures. A systematic investigation of the structure and bonding evolution is carried out with complementary characterization methods, which helps to build a model of the transformation that can be used in further high-pressure/high-temperature (high p,T) synthesis of novel nano-carbon systems for advanced applications. The amorphous carbon materials produced have the potential of accomplishing the demanding optoelectronic applications that diamond and graphene cannot achieve.
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| 5. |
- Lin, Zhenquan, et al.
(författare)
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Characterization of cross-species transcription and splicing from Penicillium to Saccharomyces cerevisiae
- 2021
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Ingår i: Journal of Industrial Microbiology and Biotechnology. - : Oxford University Press (OUP). - 1367-5435 .- 1476-5535. ; 48:9-10
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Tidskriftsartikel (refereegranskat)abstract
- Heterologous expression of eukaryotic gene clusters in yeast has been widely used for producing high-value chemicals and bioactive secondary metabolites. However, eukaryotic transcription cis-elements are still undercharacterized, and the cross-species expression mechanism remains poorly understood. Here we used the whole expression unit (including original promoter, terminator, and open reading frame with introns) of orotidine 5'-monophosphate decarboxylases from 14 Penicillium species as a showcase, and analyzed their cross-species expression in Saccharomyces cerevisiae. We found that pyrG promoters from the Penicillium species could drive URA3 expression in yeast, and that inefficient cross-species splicing of Penicillium introns might result in weak cross-species expression. Thus, this study demonstrates cross-species expression from Penicillium to yeast, and sheds light on the opportunities and challenges of cross-species expression of fungi expression units and gene clusters in yeast without refactoring for novel natural product discovery.
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| 6. |
- Zhang, Shuangshuang, et al.
(författare)
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Discovery of carbon-based strongest and hardest amorphous material
- 2022
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Ingår i: National Science Review. - : Oxford University Press. - 2095-5138 .- 2053-714X. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Carbon is one of the most fascinating elements due to its structurally diverse allotropic forms stemming from its bonding varieties (sp, sp2, and sp3). Exploring new forms of carbon has always been the eternal theme of scientific research. Herein, we report the amorphous (AM) carbon materials with high fraction of sp3 bonding recovered from compression of fullerene C60 under high pressure and high temperature previously unexplored. Analysis of photoluminescence and absorption spectra demonstrates that they are semiconducting with a bandgap range of 1.5–2.2 eV, comparable to that of widely used amorphous silicon. Comprehensive mechanical tests demonstrate that the synthesized AM-III carbon is the hardest and strongest amorphous material known so far, which can scratch diamond crystal and approach its strength. The produced AM carbon materials combine outstanding mechanical and electronic properties, and may potentially be used in photovoltaic applications that require ultrahigh strength and wear resistance.
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