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- Liu, Quanli, 1988, et al.
(författare)
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Rewiring carbon metabolism in yeast for high level production of aromatic chemicals
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The production of bioactive plant compounds using microbial hosts is considered a safe, cost-competitive and scalable approach to their production. However, microbial production of some compounds like aromatic amino acid (AAA)-derived chemicals, remains an outstanding metabolic engineering challenge. Here we present the construction of a Saccharomyces cerevisiae platform strain able to produce high levels of p-coumaric acid, an AAA-derived precursor for many commercially valuable chemicals. This is achieved through engineering the AAA biosynthesis pathway, introducing a phosphoketalose-based pathway to divert glycolytic flux towards erythrose 4-phosphate formation, and optimizing carbon distribution between glycolysis and the AAA biosynthesis pathway by replacing the promoters of several important genes at key nodes between these two pathways. This results in a maximum p-coumaric acid titer of 12.5 g L−1 and a maximum yield on glucose of 154.9 mg g−1.
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| 2. |
- Dabirian, Yasaman, 1992, et al.
(författare)
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Expanding the Dynamic Range of a Transcription Factor-Based Biosensor in Saccharomyces cerevisiae
- 2019
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Ingår i: ACS Synthetic Biology. - : American Chemical Society (ACS). - 2161-5063. ; 8:9, s. 1968-1975
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Tidskriftsartikel (refereegranskat)abstract
- Metabolite biosensors are useful tools for high-throughput screening approaches and pathway regulation approaches. An important feature of biosensors is the dynamic range. To expand the maximum dynamic range of a transcription factor-based biosensor in Saccharomyces cerevisiae, using the fapO/FapR system from Bacillus subtilis as an example case, five native promoters, including constitutive and glucose-regulated ones, were modified. By evaluating different binding site (BS) positions in the core promoters, we identified locations that resulted in a high maximum dynamic range with low expression under repressed conditions. We further identified BS positions in the upstream element region of the TEF1 promoter that did not influence the native promoter strength but resulted in repression in the presence of a chimeric repressor consisting of FapR and the yeast repressor Mig1. These modified promoters with broad dynamic ranges will provide useful information for the engineering of future biosensors and their use in complex genetic circuits.
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