Rosmarinic acid (RA) is a valuable natural product for its significant antioxidative activity, which is mainly derived from plants or by chemical synthesis. With the development of biotechnology, the research on the production of RA by microbial cell factory has attracted more attention. In this study, we engineered Saccharomyces cerevisiae to produce RA by constructing a de novo RA synthesis pathway which utilized two cytochrome P450s from Salvia miltiorrhiza Bunge and Coleus scutellarioides (L.) Benth. Through reinforcing NAD(P)H regeneration by overexpression of zwf1 and integration of ARO4K229L and ARO7G141S into the genome, the engineered S. cerevisiae produced 4.92 mg/L of RA, 8.2-fold of the control, in shake flask fermentation. The titer of RA reached 11.3 mg/L by fed-batch fermentation in 5 L bioreactor. This study increased the production of RA by combination cofactor and pathway engineering, revealed the diversity of RA synthesis in S. cerevisiae, and also provided a reference for the synthesis and accumulation of other active components 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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