ArticleMicrobial cell factories2015
Adaptive mutations in sugar metabolism restore growth on glucose in a pyruvate decarboxylase negative yeast strain.
Article in Microbial cell factories, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 43 citations in OpenAlex.
- Mechanistic and applied study of phosphofructokinases, the "gatekeeper" of the glycolytic pathway on the central carbon metabolism.Metabolic engineering communications · 2026Article
- The advances in creating Crabtree-negative Saccharomyces cerevisiae and the application for chemicals biosynthesis.FEMS yeast research · 2025Review
- Metabolic Engineering and Process Intensification for Muconic Acid Production UsingInternational journal of molecular sciences · 2024Article
- A highly efficient transcriptome-based biosynthesis of non-ethanol chemicals in Crabtree negative Saccharomyces cerevisiae.Biotechnology for biofuels and bioproducts · 2023Article
- Rewiring regulation on respiro-fermentative metabolism relieved Crabtree effects inSynthetic and systems biotechnology · 2022Article
- In-situ muconic acid extraction reveals sugar consumption bottleneck in a xylose-utilizing Saccharomyces cerevisiae strain.Microbial cell factories · 2021Article
- Corrigendum to "Rewiring yeast metabolism to synthesize products beyond ethanol" [Curr Opin Chem Biol 59 (December 2020) 182-192].Current opinion in chemical biology · 2020Article
- Rewiring yeast metabolism to synthesize products beyond ethanol.Current opinion in chemical biology · 2020Review
- Creating an oil yeast from brewing yeast.Synthetic and systems biotechnology · 2018Article
- Effect of Temperature-Shift and Temperature-Constant Cultivation on the Monacolin K Biosynthetic Gene Cluster Expression inFood technology and biotechnology · 2017Article
- GSF2 deletion increases lactic acid production by alleviating glucose repression in Saccharomyces cerevisiae.Scientific reports · 2016Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundA Saccharomyces cerevisiae strain carrying deletions in all three pyruvate decarboxylase (PDC) genes (also called Pdc negative yeast) represents a non-ethanol producing platform strain for the production of pyruvate derived biochemicals. However, it cannot grow on glucose as the sole carbon source, and requires supplementation of C2 compounds to the medium in order to meet the requirement for cytosolic acetyl-CoA for biosynthesis of fatty acids and ergosterol.
resultsIn this study, a Pdc negative strain was adaptively evolved for improved growth in glucose medium via serial transfer, resulting in three independently evolved strains, which were able to grow in minimal medium containing glucose as the sole carbon source at the maximum specific rates of 0.138, 0.148, 0.141 h(-1), respectively. Several genetic changes were identified in the evolved Pdc negative strains by genomic DNA sequencing. Among these genetic changes, 4 genes were found to carry point mutations in at least two of the evolved strains: MTH1 encoding a negative regulator of the glucose-sensing signal transduction pathway, HXT2 encoding a hexose transporter, CIT1 encoding a mitochondrial citrate synthase, and RPD3 encoding a histone deacetylase. Reverse engineering of the non-evolved Pdc negative strain through introduction of the MTH1 (81D) allele restored its growth on glucose at a maximum specific rate of 0.053 h(-1) in minimal medium with 2% glucose, and the CIT1 deletion in the reverse engineered strain further increased the maximum specific growth rate to 0.069 h(-1).
conclusionsIn this study, possible evolving mechanisms of Pdc negative strains on glucose were investigated by genome sequencing and reverse engineering. The non-synonymous mutations in MTH1 alleviated the glucose repression by repressing expression of several hexose transporter genes. The non-synonymous mutations in HXT2 and CIT1 may function in the presence of mutated MTH1 alleles and could be related to an altered central carbon metabolism in order to ensure production of cytosolic acetyl-CoA in the Pdc negative strain.
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