Optimizing central carbon metabolism (CCM) represents an attractive and challenging strategy to improve the biosynthesis of valuable chemicals due to the complex regulation of the CCM in yeast. In this study, we triggered the similar Warburg effect of cancer cells in yeast strains by introducing the human hypoxia-inducible factor-1 (HIF1) complex, which regulated the expression of numerous enzymes involved in CCM and redirected the metabolic flux from glycolysis to tricarboxylic acid cycle. This redirection promoted the production of squalene to a 2.7-fold increase than the control strain BY4741. Furthermore, the HIF1 complex boosted the production of represented endogenous triterpenoid ergosterol to 1145.95 mg/L, and exogenous triterpenoid lupeol to 236.35 mg/L in shake flask cultivation, 10.5-fold and 9.2-fold increase than engineered strains without HIF1 complex integration, respectively. This study provides a novel strategy for optimizing CCM by HIF1 mediated Warburg effect of cancer cells to improve biosynthesis of triterpenoids in yeast.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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Evidence ID | Analyze ID | File | Description |
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