This study aimed to develop an efficient Saccharomyces cerevisiae-based cell factory for heme production. The industrial strain S. cerevisiae KCCM 12638, a starter strain used in American whisky production, was selected for its naturally high heme concentration, and its medium composition was optimized. Next, CRISPR/Cas9-based genome editing was employed to enhance carbon flux through the heme biosynthetic pathway by overexpressing HEM2, HEM3, HEM12, and HEM13 genes, which encode key enzymes involved in heme synthesis. Additionally, the HMX1 gene, which encodes heme oxygenase 1, was inactivated to prevent heme degradation. The resulting ΔHMX1_H2/3/12/13 strain achieved a heme titer of 9 mg/L in batch fermentation, a 1.7-fold improvement over the wild-type KCCM 12638 strain. In a glucose-limited fed-batch fermentation, the ΔHMX1_H2/3/12/13 strain produced 67 mg/L heme. This study demonstrates that engineering industrial yeast strains can significantly enhance heme production, with promising applications in food, pharmaceuticals, and bioenergy.
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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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