ArticleACS synthetic biology2018
Yield Improvement of the Anti-MRSA Antibiotics WAP-8294A by CRISPR/dCas9 Combined with Refactoring Self-Protection Genes in Lysobacter enzymogenes OH11.
Article in ACS synthetic biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 32 citations in OpenAlex.
- Development of Efficient Expression Systems for Bacteriolytic Proteases L1 and L5 ofInternational journal of molecular sciences · 2025Article
- Current Knowledge on CRISPR Strategies Against Antimicrobial-Resistant Bacteria.Antibiotics (Basel, Switzerland) · 2024Review
- The rise and future of CRISPR-based approaches for high-throughput genomics.FEMS microbiology reviews · 2024Review
- The Transcription Regulator GntR/HutC Regulates Biofilm Formation, Motility and Stress Tolerance in Lysobacter capsici X2-3.Current microbiology · 2023Article
- Novel indole-mediated potassium ion import system confers a survival advantage to the Xanthomonadaceae family.The ISME journal · 2022Article
- The First Homologous Expression System for the β-Lytic Protease ofInternational journal of molecular sciences · 2022Article
- CRISPR-Based Approaches for Gene Regulation in Non-Model Bacteria.Frontiers in genome editing · 2022Review
- Article
- Characterisation of the Antibiotic Profile ofMicroorganisms · 2021Article
- Programmable CRISPR-Cas transcriptional activation in bacteria.Molecular systems biology · 2020Article
- Systematic optimization for production of the anti-MRSA antibiotics WAP-8294A in an engineered strain of Lysobacter enzymogenes.Microbial biotechnology · 2019Article
- CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool.Antibiotics (Basel, Switzerland) · 2019Review
- Spermidine-Regulated Biosynthesis of Heat-Stable Antifungal Factor (HSAF) inFrontiers in microbiology · 2018Article
- Boosting Secondary Metabolite Production and Discovery through the Engineering of Novel Microbial Biosensors.BioMed research international · 2018Review
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The cyclic lipodepsipeptides WAP-8294A are antibiotics with potent activity against methicillin-resistant Staphylococcus aureus (MRSA). One member of this family, WAP-8294A2 (Lotilibcin), was in clinical trials due to its high activity and distinct chemistry. However, WAP-8294A compounds are produced in a very low yield by Lysobacter and only under very stringent conditions. Improving WAP-8294A yield has become very critical for research and application of these anti-MRSA compounds. Here, we report a strategy to increase WAP-8294A production. We first used the CRISPR/dCas9 system to increase the expression of five cotranscribed genes (orf1-5) in the WAP gene cluster, by fusing the omega subunit of RNA polymerase with dCas9 that targets the operon's promoter region. This led to the transcription of the genes increased by 5-48 folds in strain dCas9-ω3. We then refactored four putative self-protection genes (orf6, orf7, orf9 and orf10) by reorganizing them into an operon under the control of a strong Lysobacter promoter, P
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