Background: Gene expression noise (variation in gene expression among individual cells of a genetically uniform cell population) can result in heterogenous metabolite production by industrial microorganisms, with cultures containing both low- and high-producing cells. The presence of low-producing individuals may be a factor limiting the potential for high yields. This study tested the hypothesis that low-producing variants in yeast cell populations can be continuously counter-selected, to increase net production of glutathione (GSH) as an exemplar product.
Results: A counter-selection system was engineered in Saccharomyces cerevisiae based on the known feedback inhibition of gamma-glutamylcysteine synthetase (GSH1) gene expression, which is rate limiting for GSH synthesis: the GSH1 ORF and the counter-selectable marker GAP1 were expressed under control of the TEF1 and GSH-regulated GSH1 promoters, respectively. An 18% increase in the mean cellular GSH level was achieved in cultures of the engineered strain supplemented with D-histidine to counter-select cells with high GAP1 expression (i.e. low GSH-producing cells). The phenotype was non-heritable and did not arise from a generic response to D-histidine, unlike that with certain other test-constructs prepared with alternative markers.
Conclusions: The results corroborate that the system developed here improves GSH production by targeting low-producing cells. This supports the potential for exploiting end-product/promoter interactions to enrich high-producing cells in phenotypically heterogeneous populations, in order to improve metabolite production by yeast.
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http://dx.doi.org/10.1186/s12934-024-02536-5 | DOI Listing |
Cancer Cell Int
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Department of Applied Chemistry, Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Puli, Taiwan.
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Zhengzhou Tobacco Research Institute of CNTC, No. 2 Fengyang Street, Zhengzhou, 450001, Henan Province, China.
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View Article and Find Full Text PDFInt J Antimicrob Agents
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Department of Life Sciences, Centre for Functional Ecology, Associate Laboratory TERRA, Faculty of Sciences and Technology, University of Coimbra, 3000-456, Coimbra, Portugal.
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View Article and Find Full Text PDFEnviron Toxicol Pharmacol
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Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou450003, Henan, China. Electronic address:
Cleft palate is the most prevalent congenital condition. Cleft palate is brought on by an exogenous chemical called all-trans retinoic acid (atRA). In order to indirectly control gene expression, long chain non-coding RNAs (lncRNAs) act as competitive endogenous RNA (ceRNA) sponges.
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December 2024
Department of Respiratory Medicine, Jinling Hospital, Nanjing Medical University, Jiangsu Province, China. Electronic address:
Circular RNA (circRNA) can sponge miRNA participate in the tumorigenesis and progression of various cancers. We substantiate for the first time that the fusion circular RNA (F-circRNA) F-circEA1 is involved in driving the echinoderm microtubule associated-protein like 4-anaplastic lymphoma kinase variant 1-positive (EML4-ALK1) lung adenocarcinoma (LUAD) progression and the expression of the parental gene EML4-ALK1, molecular mechanisms of F-circEA1 in the EML4-ALK1 LUAD remain unknown. Bioinformatics analysis showed that only miR-4673 can bind to F-circEA1 and bind to EML4-ALK1 3'-UTR to regulate the expression of EML4-ALK1.
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