ArticleNature communications2021
Gene editing enables rapid engineering of complex antibiotic assembly lines.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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Who cites it
27 citing papers in PubMed.
- Resilience of recombinant antibiotic resistance gene-containing plasmids against common cell culture disposal methods.Cell reports methods · 2026Article
- Alternative enzymatic pathways to penicillin antibiotics.Nature communications · 2026Article
- Mapping the nonribosomal specificity code through promiscuity-guided A-domain engineering.Chemical science · 2026Article
- Lipopeptide Engineering: From Natural Origins to Rational Design Against Antimicrobial Resistance.Antibiotics (Basel, Switzerland) · 2026Review
- Construction and Diversification of Natural Product Biosynthetic Gene Clusters at High Efficiency and Accuracy.ACS synthetic biology · 2025Article
- Application of multiple genomic-editing technologies inSynthetic and systems biotechnology · 2025Article
- Cyanobacterial Peptides in Anticancer Therapy: A Comprehensive Review of Mechanisms, Clinical Advances, and Biotechnological Innovation.Marine drugs · 2025Review
- 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
- Synthetic Biology in Natural Product Biosynthesis.Chemical reviews · 2025Review
- Metabolic engineering approaches for the biosynthesis of antibiotics.Microbial cell factories · 2025Review
- CRISPR/Cas9-Engineering for Increased Amylolytic Potential of Microbes for Sustainable Wastewater Treatment: A Review.Current microbiology · 2024Review
- Natural diversifying evolution of nonribosomal peptide synthetases in a defensive symbiont reveals nonmodular functional constraints.PNAS nexus · 2024Article
- Functional Diversity and Engineering of the Adenylation Domains in Nonribosomal Peptide Synthetases.Marine drugs · 2024Review
- Multiple pathways impact the swarming motility ofMicrobiology spectrum · 2024Article
- High-throughput reprogramming of an NRPS condensation domain.Nature chemical biology · 2024Article
- Controlling Substrate- and Stereospecificity of Condensation Domains in Nonribosomal Peptide Synthetases.ACS chemical biology · 2024Article
- Metagenomic domain substitution for the high-throughput modification of nonribosomal peptides.Nature chemical biology · 2024Article
- Multiple Pathways Impact Swarming Motility ofbioRxiv : the preprint server for biology · 2024Article
- Synthetic ramoplanin analogues are accessible by effective incorporation of arylglycines in solid-phase peptide synthesis.Chemical science · 2023Article
- Guidelines for Optimizing Type S Nonribosomal Peptide Synthetases.ACS synthetic biology · 2023Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Re-engineering biosynthetic assembly lines, including nonribosomal peptide synthetases (NRPS) and related megasynthase enzymes, is a powerful route to new antibiotics and other bioactive natural products that are too complex for chemical synthesis. However, engineering megasynthases is very challenging using current methods. Here, we describe how CRISPR-Cas9 gene editing can be exploited to rapidly engineer one of the most complex megasynthase assembly lines in nature, the 2.0 MDa NRPS enzymes that deliver the lipopeptide antibiotic enduracidin. Gene editing was used to exchange subdomains within the NRPS, altering substrate selectivity, leading to ten new lipopeptide variants in good yields. In contrast, attempts to engineer the same NRPS using a conventional homologous recombination-mediated gene knockout and complementation approach resulted in only traces of new enduracidin variants. In addition to exchanging subdomains within the enduracidin NRPS, subdomains from a range of NRPS enzymes of diverse bacterial origins were also successfully utilized.
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