ArticleNature communications2024
Engineered cytosine base editor enabling broad-scope and high-fidelity gene editing in Streptomyces.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Multiplexed CRISPR base editing enables pulse-activated irreversible biocontainment of engineered bacteria.Nucleic acids research · 2026Article
- Occurrence and applications of CRISPR-Cas systems in bifidobacteria.Applied and environmental microbiology · 2026Review
- Comparative genomic and phenotypic analysis of Streptomyces rochei SOSIST-3 isolated from the Southern Ocean.Molecular biology reports · 2026Article
- Integrated multi-omics and genome mining strategies for activating cryptic polyketide biosynthetic gene clusters inFrontiers in microbiology · 2026Review
- Research progress of base editing and prime editing tools based on the CRISPR/Cas system.Molecular therapy. Nucleic acids · 2025Review
- STAGE: A compact and versatile TnpB-based genome editing toolkit forProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Application of multiple genomic-editing technologies inSynthetic and systems biotechnology · 2025Article
- Identification of a critical gene involved in the biosynthesis of the polyene macrolide lavencidin inApplied and environmental microbiology · 2025Article
- Engineering of Peptide-Inserted Base Editors with Enhanced Accuracy and Security.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Metabolic engineering approaches for the biosynthesis of antibiotics.Microbial cell factories · 2025Review
- One-for-all gene inactivation via PAM-independent base editing in bacteria.The Journal of biological chemistry · 2025Article
- Next-generation CRISPR technology for genome, epigenome and mitochondrial editing.Transgenic research · 2024Review
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Authors and funding
9 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Base editing (BE) faces protospacer adjacent motif (PAM) constraints and off-target effects in both eukaryotes and prokaryotes. For Streptomyces, renowned as one of the most prolific bacterial producers of antibiotics, the challenges are more pronounced due to its diverse genomic content and high GC content. Here, we develop a base editor named eSCBE3-NG-Hypa, tailored with both high efficiency and -fidelity for Streptomyces. Of note, eSCBE3-NG-Hypa recognizes NG PAM and exhibits high activity at challenging sites with high GC content or GC motifs, while displaying minimal off-target effects. To illustrate its practicability, we employ eSCBE3-NG-Hypa to achieve precise key amino acid conversion of the dehydratase (DH) domains within the modular polyketide synthase (PKS) responsible for the insecticide avermectins biosynthesis, achieving domains inactivation. The resulting DH-inactivated mutants, while ceasing avermectins production, produce a high yield of oligomycin, indicating competitive relationships among multiple biosynthetic gene clusters (BGCs) in Streptomyces avermitilis. Leveraging this insight, we use eSCBE3-NG-Hypa to introduce premature stop codons into competitor gene cluster of ave in an industrial S. avermitilis, with the mutant Δolm exhibiting the highest 4.45-fold increase in avermectin B1a compared to the control. This work provides a potent tool for modifying biosynthetic pathways and advancing metabolic engineering in Streptomyces.
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