Background: The application of synthetic biology techniques has been recognized as an efficient alternative for the biosynthesis of high-value natural products, and various metabolic engineering strategies have been employed to develop microbial cell factories. However, exploration of more efficient metabolic pathway optimization strategies is still required to further improve the producing potential of microbial cell factories to meet the industrial requirements.
Results: In this study, we found that the introduction of human N6,2'-O-dimethyladenosine (m6Am) methyltransferase PCIF1 into Saccharomyces cerevisiae significantly promoted the biosynthesis of squalene, increased by 2.3-fold. Transcriptome analysis revealed that PCIF1 upregulated genes associated with glycolysis and acetyl-CoA biosynthesis pathways, and also activated the cell wall integrity mitogen-activated protein kinase (MAPK) pathway to improve the cell wall stress response. Importantly, PCIF1 expression notably enhanced squalene and sesquiterpenoid longifolene production in engineered yeast strains, with 2.3-fold and 1.4-fold higher increase, respectively.
Conclusion: This study presents a PCIF1-based metabolic engineering strategy that could serve as an effective approach for the optimization of terpene biosynthesis in yeast cell factories.
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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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