Ursolic acid (UA) and oleanolic acid (OA) have been demonstrated to have promising therapeutic potential as anticancer and bacteriostasis agents. Herein, via the heterologous expression and optimization of CrAS, CrAO, and AtCPR1, the de novo syntheses of UA and OA were achieved with titers of 7.4 and 3.0 mg/L, respectively. Subsequently, metabolic flux was redirected by increasing the cytosolic acetyl-CoA level and tuning the copy numbers of ERG1 and CrAS, thereby affording 483.4 mg/L UA and 163.8 mg/L OA. Furthermore, the lipid droplet compartmentalization of CrAO and AtCPR1 alongside the strengthening of the NADPH regeneration system increased the UA and OA titers to 692.3 and 253.4 mg/L in a shake flask and to 1132.9 and 433.9 mg/L in a 3-L fermenter, which is the highest UA titer reported to date. Overall, this study provides a reference for constructing microbial cell factories that can efficiently synthesize terpenoids.
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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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