ArticleNature communications2020
In vitro Cas9-assisted editing of modular polyketide synthase genes to produce desired natural product derivatives.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- Advances in large DNA fragment assembly for microbial cell factory engineering.Quantitative biology (Beijing, China) · 2026Review
- Skeletal editing via multi-step engineering of a modular polyketide synthase.Nature communications · 2026Article
- Application of edible fungi in gut microbiota regulation.NPJ science of food · 2025Review
- Plug-and-play engineering of modular polyketide synthases.Nature chemical biology · 2025Article
- iCASRED, a scarless DNA editing tool inSynthetic and systems biotechnology · 2025Article
- Expanding catalytic versatility of modular polyketide synthases for alcohol biosynthesis.Nature chemical biology · 2025Article
- A CRISPR-Cas9 system for knock-out and knock-in of high molecular weight DNA enables module-swapping of the pikromycin synthase in its native host.Microbial cell factories · 2025Article
- Engineered CRISPR-Cas9 for Streptomyces sp. genome editing to improve specialized metabolite production.Nature communications · 2025Article
- Refactoring the pikromycin synthase for the modular biosynthesis of macrolide antibiotics in E. coli.Research square · 2025Article
- Seamless site-directed mutagenesis in complex cloned DNA sequences using the RedEx method.Nature protocols · 2024Review
- Enhancement of acyl-CoA precursor supply for increased avermectin B1a production by engineering meilingmycin polyketide synthase and key primary metabolic pathway genes.Microbial biotechnology · 2024Article
- Application and development of CRISPR technology in the secondary metabolic pathway of the active ingredients of phytopharmaceuticals.Frontiers in plant science · 2024Review
- Current State-of-the-Art Toward Chemoenzymatic Synthesis of Polyketide Natural Products.Chembiochem : a European journal of chemical biology · 2023Review
- Precise DNA cleavage using CRISPR-SpRYgests.Nature biotechnology · 2023Article
- Insights into azalomycin F assembly-line contribute to evolution-guided polyketide synthase engineering and identification of intermodular recognition.Nature communications · 2023Article
- Recent developments in the identification and biosynthesis of antitumor drugs derived from microorganisms.Engineering microbiology · 2022Review
- Breaking the Bottleneck in Anticancer Drug Development: Efficient Utilization of Synthetic Biology.Molecules (Basel, Switzerland) · 2022Review
- Understanding and Manipulating Assembly Line Biosynthesis by Heterologous Expression in Streptomyces.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Gene editing enables rapid engineering of complex antibiotic assembly lines.Nature communications · 2021Article
- The intriguing chemistry and biology of sulfur-containing natural products from marine microorganisms (1987-2020).Marine life science & technology · 2021Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One major bottleneck in natural product drug development is derivatization, which is pivotal for fine tuning lead compounds. A promising solution is modifying the biosynthetic machineries of middle molecules such as macrolides. Although intense studies have established various methodologies for protein engineering of type I modular polyketide synthase(s) (PKSs), the accurate targeting of desired regions in the PKS gene is still challenging due to the high sequence similarity between its modules. Here, we report an innovative technique that adapts in vitro Cas9 reaction and Gibson assembly to edit a target region of the type I modular PKS gene. Proof-of-concept experiments using rapamycin PKS as a template show that heterologous expression of edited biosynthetic gene clusters produced almost all the desired derivatives. Our results are consistent with the promiscuity of modular PKS and thus, our technique will provide a platform to generate rationally designed natural product derivatives for future drug development.
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