Background: Lactic acid is a highly versatile molecule whose increasing demand across the polymer, food, pharmaceutical, chemical, and cosmetics industries underscores its industrial and economic significance. Currently, lactic acid is predominantly produced via microbial fermentation using lactic acid bacteria facing limitations such as sensitivity to low pH, complex nutritional requirement and waste product generation during downstream processing.
Results: To address these challenges, we employed a genetically modified Saccharomyces cerevisiae strain capable of producing lactic acid and subjected it to long-term adaptive laboratory evolution. The strain was cultured in serial shake flask cultivations over a period of 35 months under elevating lactic acid concentrations and increasing stress to low pH. The evolved populations showed improved production of up to 250% in final lactic acid titers compared to the parental strain. The best-performing strains reached 67 g L⁻¹ at a final pH of 2.4 without pH control or 165 g L⁻¹ lactic acid at pH 3.0 with the addition of pH neutralizers, representing - to our knowledge - the highest LA titer reported in shake flask cultivations for S. cerevisiae.
Conclusion: Overall, our results prove the great potential of long-term adaptive laboratory evolution in developing robust yeast cell factories for industrial organic acid production.
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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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