Asiatic acid, a bioactive component of Centella asiatica (L.) Urban, exhibits plentiful valuable pharmacological properties. Herein, we engineered Saccharomyces cerevisiae to produce asiatic acid. Initially, asiatic acid was synthesized by expressing the Centella asiatica cytochrome P450 monooxygenases CYP714E19 and CYP716C11 in a Saccharomyces cerevisiae strain optimized for ursolic acid production. The engineered strain yielded 0.42 ± 0.01 mg/L and 0.067 ± 0.0013 mg/g dry cell weight (DCW) of asiatic acid. Subsequently, a suitable cytochrome P450 reductase was screened, and key enzymes were overexpressed to effectively convert ursolic acid to asiatic acid. Strengthening heme biosynthesis, promoting endoplasmic reticulum (ER) expansion, and enhancing the cofactor supply were implemented to improve P450 catalytic activity. Additionally, a PDZ-PDZlig-mediated protein self-assembly strategy was used to improve the efficiency of the CYP714E19 and CYP716C11 catalytic cascade. Finally, the highest production was achieved (30.09 ± 0.15 mg/L, 4.09 ± 0.01 mg/g DCW) in microbial cell factories. This work establishes a foundation for efficient production of asiatic acid.
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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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